B cells are
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s that play a large role in the
humoral immune responseThe Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
(as opposed to the
cell-mediated immune responseCell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
, which is governed by
T cellT cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s). The principal functions of B cells are to make
antibodiesAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against
antigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s, perform the role of
antigen-presenting cellAn antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
s (APCs) and eventually develop into memory B cells after activation by antigen interaction. B cells are an essential component of the
adaptive immune systemThe adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
.
The abbreviation "B", in B cell, comes from the
bursa of FabriciusIn birds, the bursa of Fabricius is the site of hematopoiesis, a specialized organ that, as first demonstrated by Bruce Glick and later by Max Cooper and Robert Good, is necessary for B cell development in birds...
in birds, where they mature. In mammals, immature B cells are formed in the
bone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, which is used as a
backronymA backronym or bacronym is a phrase constructed purposely, such that an acronym can be formed to a specific desired word. Backronyms may be invented with serious or humorous intent, or may be a type of false or folk etymology....
for the cells' name.
Development of B cells
Immature B cells are produced in the
bone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
of most mammals.
RabbitRabbits are small mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world...
s are an exception; their B cells develop in the appendix-sacculus rotundus. After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to the spleen, where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes.
B cell development occurs through several stages, each stage representing a change in the genome content at the antibody
lociIn the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
. An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region. In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.
| Stage |
Heavy chain ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...
|
Light chain ]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
|
Ig |
IL-7 receptor The interleukin-7 receptor is a protein found on the surface of cells. It is made up of two different smaller protein chains - i.e. it is a heterodimer, and consists of two subunits, interleukin-7 receptor-α and common-γ chain receptor . The common-γ chain receptors is shared with various...
? |
| CD19 B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...
?
|-
| Progenitor (or pre-pro) B cells |
germline In biology and genetics, the germline of a mature or developing individual is the line of germ cells that have genetic material that may be passed to a child.For example, gametes such as the sperm or the egg, are part of the germline...
|
| germline |
- |
Yes |
|
>-
| Early Pro (or pre-pre)-B cells
undergoes D-J rearrangement |
germline |
- |
Yes |
|
>-
| Late Pro (or pre-pre)-B cells
undergoes V-DJ rearrangement |
germline |
- |
Yes |
|
>-
| Large Pre-B cellA Pre-B cell is a precursor to the development of B cells.Certain leukemias/lymphomas are associated with immature B cells, and observing pre-B cell populations can be useful in the identification of these conditions....
s
is VDJ rearranged |
germline |
IgM IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
in cytoplasm |
Yes |
|
>-
| Small Pre-B cells
is VDJ rearranged |
undergoes V-J rearrangement |
IgM IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
in cytoplasm |
Yes |
|
>-
| Immature B cells
is VDJ rearranged |
VJ rearranged |
IgM IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
on surface |
No |
|
>-
| Mature B cells
is VDJ rearranged |
VJ rearranged |
IgM IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
and IgDIGD can refer to:*Internet Gateway Device as defined in UPnP.*İGD, İlerici Gençler Derneği, Progressive Young Association of Turkey*Immunoglobulin D, an antibody protein involved in the maturation of B cells....
on surface |
No |
Yes |
When the B cell fails in any step of the maturation process, it will die by a mechanism called
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, here called
clonal deletionClonal deletion is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes.It is one method of immune tolerance....
. B cells are continuously produced in the bone marrow. When B cell receptors on the surface of the cell matches the detected antigens present in the body, the B cell proliferates and secretes a free form of those receptors (antibodies) with identical binding sites as the ones on the original cell surface. After activation, the cell proliferates and B memory cells would form to recognise the same antigen. This information would then be used as a part of the adaptive immune system for a more efficient and more powerful immune response for future encounters with that antigen.
B cell membrane receptors evolve and change throughout the B cell life span. TACI,
BCMA-Interactions:TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B. A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.-Further reading:...
and BAFF-R are present on both immature B cells and mature B cells. All of these 3 receptors may be inhibited by
BelimumabBelimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator , also known as B cell activation factor of the TNF family...
.
CD20B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
is expressed on all stages of B cell development except the first and last; it is present from pre-B cells through memory cells, but not on either pre-pro-B cells or plasma cells.
Immune Tolerance
Like their fellow lymphocytes, the T cells, immature B cells are tested for auto-reactivity by the immune system before leaving the bone marrow. In the bone marrow (the central lymphoid organ), central tolerance is produced. The immature B cells whose B cell Receptors (BCRs) bind too strongly to self antigens will not be allowed to mature. If B cells are found to be highly reactive to self, three mechanisms can occur.
- Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self antigen specificity.
- Receptor editing: the BCRs of self reactive B cells are given an opportunity to rearrange their conformation. This process occurs via the continued expression of the Recombination activating gene
The recombination activating genes encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination...
(RAG). Through the help of RAG, receptor editing involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to produce a BCR that is less autoreactive, apoptosis will occur. Note that defects in the RAG-1 and RAG-2 genes are implicated in Severe Combined ImmunodeficiencySevere combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(SCID). The inability to recombine and generate new receptors lead to failure of maturity for both B cells and T cells.
- Anergy: B cells enter a state of permanent unresponsiveness when they bind with weakly cross-linking self antigens that are small and soluble.
Functions
The human body makes millions of different types of B cells each day that circulate in the
bloodBlood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
and
lymphatic systemThe lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...
performing the role of immune surveillance. They do not produce antibodies until they become fully activated. Each B cell has a unique receptor
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
(referred to as the B cell receptor (BCR)) on its surface that will bind to one particular
antigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
. The BCR is a membrane-bound immunoglobulin, and it is this
moleculeA molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
that allows the distinction of B cells from other types of
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
, as well as being the main
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
involved in B cell activation. Once a B cell encounters its cognate antigen and receives an additional signal from a
T helper cellT helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
, it can further differentiate into one of the two types of B cells listed below (plasma B cells and
memory B cellMemory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...
s). The B cell may either become one of these
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
types directly or it may undergo an intermediate differentiation step, the
germinal centerGerminal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...
reaction, where the B cell will
hypermutateSomatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...
the variable region of its immunoglobulin
geneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
("somatic hypermutation") and possibly undergo class switching. Other functions for B cells include antigen presentation, cytokine production and lymphoid tissue organization.
Clonality
B cells exist as
clonesA clone is a group of identical cells that share a common ancestry, meaning they are derived from the same mother cell.Clonality implies the state of a cell or a substance being derived from one source or the other...
. All B cells derive from a particular cell, and thus, the antibodies their differentiated progenies (see below) produce can recognize and/or bind the same specific surface components composed of biological macromolecules (
epitopeAn epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
) of a given antigen. Such clonality has important consequences, as immunogenic memory relies on it. The great diversity in immune response comes about because there are up to 10
9 clones with specificities for recognizing different antigens. A single B cell or a clone of cells with shared specificity, upon encountering its specific antigen, divides to produce many B cells. Most of such B cells differentiate into plasma cells that secrete antibodies into blood that bind the same epitope that elicited proliferation in the first place. A small minority survives as
memory cells that can recognize only the same epitope. However, with each cycle, the number of surviving memory cells
increases. The increase is accompanied by
affinity maturation which induces the survival of B cells that bind to the particular antigen with high affinity. This subsequent amplification with improved specificity of immune response is known as
secondary immune response. B cells that encounter antigen for the first time are known as
naive B cells.
B cell types
- Plasma B cells (also known as plasma cells, plasmocytes, and effector B cells) are large B cells that have been exposed to antigen and produce and secrete large amounts of antibodies
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytePhagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
s and activation of the complement systemThe complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasmThe cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. These are short lived cells and undergo apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
when the inciting agent that induced immune response is eliminated. This occurs because of cessation of continuous exposure to various colony stimulating factors required for survival.
- Memory B cell
Memory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...
s are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.
- B-1 cell
B-1 cells are a sub-class of B cell lymphocytes that are involved in the humoral immune response. They are not part of the adaptive immune system,as they have no memory, but otherwise, B-1 cells perform many of the same roles as other B cells: making antibodies against antigens and acting as...
s express IgM in greater quantities than IgG and their receptors show polyspecificity, meaning that they have low affinities for many different antigens. Polyspecific immunoglobulins often have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities.
- B-2 cells are the conventional B cells most texts refer to.
- Marginal-zone B cell
Marginal zone B cells are noncirculating mature B cells that segregate anatomically into the marginal zone of the spleen. This region contains multiple subtypes of macrophages, dendritic cells, and the MZ B cells; it is not fully formed until 2 to 3 weeks after birth in rodents and 1 to 2 years in...
s
- Follicular B Cells
Recognition of antigen by B cells
A critical difference between B cells and T cells is how each lymphocyte recognizes its
antigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
. B cells recognize their cognate antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a
peptidePeptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
fragment presented by an antigen presenting cell's
MHCMajor histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
molecule to the
T cell receptorThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
.
Activation of B cells
B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal
proliferationThe term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and terminal
differentiationIn developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
into
plasma cellPlasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
s).
B cells that have not been exposed to antigen, also known as
naïve B cells, can be activated in a T cell-dependent or -independent manner.
T cell-dependent activation
Once a
pathogenA pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
is ingested by an
antigen-presenting cellAn antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
such as a
macrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
or
dendritic cellDendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
, the pathogen's proteins are then digested to peptides and attached to a
class II MHCMajor histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
protein. This complex is then moved to the outside of the cell membrane. The macrophage is now activated to deliver multiple signals to a specific
T cellT cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
that recognizes the peptide presented. The T cell is then stimulated to produce autocrines (Refer to
Autocrine signallingAutocrine signaling is a form of signalling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on the same cell, leading to changes in the cell...
), resulting in the proliferation and differentiation to effector and memory T cells. Helper T cells (i.e. CD4+ T cells) then activate specific B cells through a phenomenon known as an
Immunological synapseIn immunology, an immunological synapse is the interface between an antigen-presenting cell and a lymphocyte. It was first discovered by Abraham Kupfer at the National Jewish Medical and Research Center in Denver and the term was coined by Michael Dustin at NYU who studied it in further detail...
. Activated B cells subsequently produce antibodies which assist in inhibiting pathogens until phagocytes (i.e. macrophages, neutrophils) or the
complement systemThe complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
for example clears the host of the pathogen(s).
Most antigens are T-dependent, meaning T cell help is required for maximal antibody production. With a T-dependent antigen, the first signal comes from antigen cross linking the B cell receptor (BCR) and the second signal comes from
co-stimulationDuring the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.- Co-stimulation T cells require :...
provided by a
T cellT cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
. T dependent antigens contain proteins that are presented on B cell Class II MHC to a special subtype of T cell called a Th2 cell. When a B cell processes and presents the
same antigen to the
primed Th cell, the T cell secretes
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s that activate the B cell. These cytokines trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG,
IgAIga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
, and
IgEIGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
and memory cell generation occur in response to T-dependent antigens. This isotype switching is known as Class Switch Recombination (CSR). Once this switch has occurred, that particular B cell will usually no longer make the earlier isotypes,
IgMIGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
or
IgDIGD can refer to:*Internet Gateway Device as defined in UPnP.*İGD, İlerici Gençler Derneği, Progressive Young Association of Turkey*Immunoglobulin D, an antibody protein involved in the maturation of B cells....
.
T cell-independent activation
Many antigens are T cell-independent in that they can deliver both of the signals to the B cell.
MiceA mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
without a
thymusThe thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
(nude or athymic mice that do not produce any T cells) can respond to T independent antigens. Many bacteria have repeating carbohydrate epitopes that stimulate B cells, by cross-linking the IgM antigen receptors in the B cell, responding with IgM synthesis in the absence of T cell help.
Conjugate vaccineA conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein , thereby conferring the immunological attributes of the carrier on the attached antigen...
s are made to provide a stronger immune response against these foreign molecules. There are two types of T cell independent activation;
Type 1 T cell-independent (polyclonal) activation, and
type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells).
The ancestral roots of B cells
In an October 2006 issue of
Nature ImmunologyNature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
, certain B cells of basal vertebrates (like
fishFish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
and
amphibianAmphibians , are a class of vertebrate animals including animals such as toads, frogs, caecilians, and salamanders. They are characterized as non-amniote ectothermic tetrapods...
s) were shown to be capable of
phagocytosis, a function usually associated with cells of the
innate immune systemThe innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
. The authors postulate that these phagocytic B cells represent the ancestral history shared between macrophages and lymphocytes. B cells may have evolved from macrophage-like cells during the formation of the
adaptive immune systemThe adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
.
B cells in humans (and other vertebrates) are nevertheless able to endocytose antibody-fixed pathogens, and it is through this route that MHC Class II presentation by B cells is possible, allowing Th2 help and stimulation of B cell proliferation. This is purely for the benefit of MHC Class II presentation, not as a significant method of reducing the pathogen load.
Origin of the term
The abbreviation "B" in B cell originally came from
Bursa of FabriciusIn birds, the bursa of Fabricius is the site of hematopoiesis, a specialized organ that, as first demonstrated by Bruce Glick and later by Max Cooper and Robert Good, is necessary for B cell development in birds...
, an organ in birds in which avian B
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
mature. When it was discovered that in most mammals immature B cells are formed in bone marrow, the word B cell continued to be used, although other blood cells also originate from pluripotent stem cells in the bone marrow. The fact that bone and bursa both start with the letter 'B' is a coincidence.
B cell-related pathology
Aberrant antibody production by B cells is implicated in many autoimmune diseases, such as rheumatoid arthritis and
systemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
. B cells are also susceptible to malignant transformation.
Additional image
See also
- Affinity maturation
In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response...
- Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
- Clonal selection
The clonal selection hypothesis has become a widely accepted model for how the immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens invading the body....
- Original antigenic sin
Original antigenic sin, also known as the Hoskins effect, refers to the propensity of the body's immune system to preferentially utilize immunological memory based on a previous infection when a second slightly different version, of that foreign entity is encountered...
External links