Plasma cell
Encyclopedia
Plasma 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
. Like all blood cells, plasma cells ultimately originate in the bone marrow
; however, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells, normally in lymph nodes.
and processed. Pieces of the pathogen (which are now known as antigenic peptides) are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called T helper cells). These T cells bind to the MHC II/antigen molecule and cause activation of the B cell.
Upon stimulation by a T cell, which usually occurs in germinal center
s of secondary lymphoid organs like the spleen and lymph nodes, the activated B cell begins to differentiate into more specialized cells. Germinal center
B cells may differentiate into memory B cells or plasma cells. The mechanism by which a B cell becomes one or the other of these three is a process known as affinity maturation. Most of these B cells will become plasmablasts, and eventually plasma cells, and begin producing large volumes of antibodies.
The most immature blood cell that is considered a plasma cell instead of a B cell is the plasmablast. Plasmablasts secrete more antibodies than B cells, but less than plasma cells. They divide rapidly and are still capable of internalizing antigens and presenting them to T cells. A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell. Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1
and IRF4
.
, cannot act as antigen-presenting cells because they no longer display MHC-II, and do not take up antigen because they no longer display significant quantities of immunoglobulin on the cell surface. However, continued exposure to antigen through those low levels of immunoglobulin is important, as it partly determines the cell's lifespan.
The lifespan, class of antibodies produced, and the location that the plasma cell moves to also depends on signals, such as cytokines, received from the T cell during differentiation. Differentiation through a T cell-independent antigen stimulation (stimulation of a B cell that does not require the involvement of a T cell) can happen anywhere in the body and results in short-lived cells that secrete IgM antibodies. The T cell-dependent processes are subdivided into primary and secondary responses: a primary response (meaning that the T cell is present at the time of initial contact by the B cell with the antigen) produces short-lived cells that remain in the extramedullary regions of lymph nodes; a secondary response produces longer-lived cells that produce IgG and IgA, and frequently travel to the bone marrow. For example, plasma cells will likely secrete IgG3 antibodies if they matured in the presence of the cytokine interferon-gamma
. Since B cell maturation also involves somatic hypermutation
(a process completed before differentiation into a plasma cell), these antibodies frequently have a very high affinity for their antigen.
Plasma cells can only produce a single kind of antibody in a single class of immunoglobulin. In other words, every B cell is specific to a single antigen, but each cell can produce several thousand matching antibodies per second. This prolific production of antibodies is an integral part of the humoral immune response.
-to-cytoplasm
ratio and a characteristic appearance on light microscopy. They have basophilic
cytoplasm and an eccentric nucleus with heterochromatin
in a characteristic cartwheel
or clock face arrangement. Their cytoplasm also contains a pale zone that on electron microscopy contains an extensive Golgi apparatus
and centriole
s (EM picture). Abundant rough endoplasmic reticulum combined with a well-developed Golgi apparatus makes plasma cells well-suited for secreting immunoglobulins.
and CD20
. Instead, plasma cells are identified through flow cytometry
by their additional expression of CD38
, CD78
, the Interleukin-6 receptor
and lack of expression of CD45
. In humans, CD27 is a good marker for plasma cells, naive B cells are CD27-, memory B-cells are CD27+ and plasma cells are CD27++.
CD38
and CD138 are expressed at high levels.
, multiple myeloma
, Waldenström macroglobulinemia
and plasma cell leukemia
are malignant neoplasms
("cancer") of the plasma cells. Multiple myeloma is frequently identified because malignant plasma cells continue producing an antibody, which can be detected as a paraprotein
.
Common variable immunodeficiency
is thought to be due to a problem in the differentiation
from lymphocytes to plasma cells. The result is a low serum antibody level and risk of infections.
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
and the lymphatic system
Lymphatic system
The 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...
. Like all blood cells, plasma cells ultimately originate in the bone marrow
Bone marrow
Bone 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...
; however, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells, normally in lymph nodes.
Development
After leaving the bone marrow, the B cell acts as an antigen presenting cell (APC) and internalizes offending antigens. That antigen is taken up by the B cell through receptor-mediated endocytosisReceptor-mediated endocytosis
Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
and processed. Pieces of the pathogen (which are now known as antigenic peptides) are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called T helper cells). These T cells bind to the MHC II/antigen molecule and cause activation of the B cell.
Upon stimulation by a T cell, which usually occurs in germinal center
Germinal center
Germinal 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...
s of secondary lymphoid organs like the spleen and lymph nodes, the activated B cell begins to differentiate into more specialized cells. Germinal center
Germinal center
Germinal 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...
B cells may differentiate into memory B cells or plasma cells. The mechanism by which a B cell becomes one or the other of these three is a process known as affinity maturation. Most of these B cells will become plasmablasts, and eventually plasma cells, and begin producing large volumes of antibodies.
The most immature blood cell that is considered a plasma cell instead of a B cell is the plasmablast. Plasmablasts secrete more antibodies than B cells, but less than plasma cells. They divide rapidly and are still capable of internalizing antigens and presenting them to T cells. A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell. Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1
PRDM1
PR domain zinc finger protein 1 also known as BLIMP-1 is a protein that in humans is encoded by the PRDM1 gene. BLIMP-1 acts as a repressor of beta-interferon gene expression. The protein binds specifically to the PRDI of the β-IFN gene promoter...
and IRF4
IRF4
Interferon regulatory factor 4 is a protein that in humans is encoded by the IRF4 gene, also known as MUM1. In melanocytic cells the IRF4 gene may be regulated by MITF.-Interactions:IRF4 has been shown to interact with STAT6, NFATC2, BCL6 and SPI1....
.
Activity
After the process of affinity maturation in germinal centers, plasma cells have an indeterminate lifespan, ranging from days to months. They secrete high levels of antibodies, ranging from hundreds to thousands of antibodies per second per cell. Unlike their precursors, they cannot switch antibody classesImmunoglobulin class switching
Immunoglobulin class switching is a biological mechanism that changes a B cell's production of antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG...
, cannot act as antigen-presenting cells because they no longer display MHC-II, and do not take up antigen because they no longer display significant quantities of immunoglobulin on the cell surface. However, continued exposure to antigen through those low levels of immunoglobulin is important, as it partly determines the cell's lifespan.
The lifespan, class of antibodies produced, and the location that the plasma cell moves to also depends on signals, such as cytokines, received from the T cell during differentiation. Differentiation through a T cell-independent antigen stimulation (stimulation of a B cell that does not require the involvement of a T cell) can happen anywhere in the body and results in short-lived cells that secrete IgM antibodies. The T cell-dependent processes are subdivided into primary and secondary responses: a primary response (meaning that the T cell is present at the time of initial contact by the B cell with the antigen) produces short-lived cells that remain in the extramedullary regions of lymph nodes; a secondary response produces longer-lived cells that produce IgG and IgA, and frequently travel to the bone marrow. For example, plasma cells will likely secrete IgG3 antibodies if they matured in the presence of the cytokine interferon-gamma
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
. Since B cell maturation also involves somatic hypermutation
Somatic hypermutation
Somatic 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...
(a process completed before differentiation into a plasma cell), these antibodies frequently have a very high affinity for their antigen.
Plasma cells can only produce a single kind of antibody in a single class of immunoglobulin. In other words, every B cell is specific to a single antigen, but each cell can produce several thousand matching antibodies per second. This prolific production of antibodies is an integral part of the humoral immune response.
Microscopic anatomy
Plasma cells are large lymphocytes with a considerable nucleusCell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
-to-cytoplasm
Cytoplasm
The 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...
ratio and a characteristic appearance on light microscopy. They have basophilic
Basophilic
Basophilic is a technical term used by histologists. It describes the microscopic appearance of cells and tissues, as seen down the microscope, after a histological section has been stained with a basic dye. The most common such dye is haematoxylin....
cytoplasm and an eccentric nucleus with heterochromatin
Heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...
in a characteristic cartwheel
Cartwheel
A cartwheel is a part of a cart. It may also mean:*Cartwheel , an acrobatic maneuver*Cartwheel Galaxy*Cart-wheel hat, worn by women*Slang term for a silver dollar coin -See also:...
or clock face arrangement. Their cytoplasm also contains a pale zone that on electron microscopy contains an extensive Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
and centriole
Centriole
A Centriole is a barrel-shaped cell structure found in most animal eukaryotic cells, though it is absent in higher plants and most fungi. The walls of each centriole are usually composed of nine triplets of microtubules...
s (EM picture). Abundant rough endoplasmic reticulum combined with a well-developed Golgi apparatus makes plasma cells well-suited for secreting immunoglobulins.
Surface antigens
Terminally differentiated plasma cells express relatively few surface antigens, and do not express common pan-B cell markers, such as CD19CD19
B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...
and CD20
CD20
B-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....
. Instead, plasma cells are identified through flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...
by their additional expression of CD38
CD38
CD38 , also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells , including CD4+, CD8+, B and natural killer cells...
, CD78
CD78
CD78 is a protein expressed on the surface of some immature and all mature B-cells. It is considered a pan-B cell antigen. Other names include Cdw78, Ba antigen, Leu21 and LO-panB-a.-Expression:...
, the Interleukin-6 receptor
Interleukin-6 receptor
Interleukin 6 receptor also known as CD126 is a type I cytokine receptor....
and lack of expression of CD45
CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen , which was originally called leukocyte common antigen.- Function :The protein encoded by this gene is a member of the protein tyrosine...
. In humans, CD27 is a good marker for plasma cells, naive B cells are CD27-, memory B-cells are CD27+ and plasma cells are CD27++.
CD38
CD38
CD38 , also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells , including CD4+, CD8+, B and natural killer cells...
and CD138 are expressed at high levels.
Role in disease
PlasmacytomaPlasmacytoma
Plasmacytoma refers to a malignant plasma cell tumor growing within soft tissue or within the skeleton. The skeletal forms usually have other occult tumors and frequently disseminate to multiple myeloma over the course of 5–10 years. The soft tissue forms most often occur in the upper respiratory...
, multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
, Waldenström macroglobulinemia
Waldenström macroglobulinemia
Waldenström's macroglobulinemia is cancer involving a subtype of white blood cells called lymphocytes. The main attributing antibody is Immunoglobulin M . WM is an "indolent lymphoma,"...
and plasma cell leukemia
Plasma cell leukemia
Plasma cell leukemia , a lymphoproliferative disorder, is a rare cancer involving a subtype of white blood cells called plasma cells. Plasma cell leukemia is one of the most aggressive human neoplasms and constitutes 2% to 4% of all cases of plasma cell disorders...
are malignant neoplasms
Hematological malignancy
Hematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
("cancer") of the plasma cells. Multiple myeloma is frequently identified because malignant plasma cells continue producing an antibody, which can be detected as a paraprotein
Paraprotein
A paraprotein is an immunoglobulin or immunoglobulin light-chain that is produced in excess by the clonal proliferation of plasma cells. Detection of paraproteins in the urine or blood is most often associated with benign MGUS , where they remain "silent", and multiple myeloma. An excess in the...
.
Common variable immunodeficiency
Common variable immunodeficiency
Common variable immunodeficiency is a group of approximately 150 primary immunodeficiencies , which have a common set of symptoms but which have different underlying causes.Common variable immunodeficiency is the most commonly encountered primary immunodeficiency.-Causes and types:CVID...
is thought to be due to a problem in the differentiation
Cellular differentiation
In 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...
from lymphocytes to plasma cells. The result is a low serum antibody level and risk of infections.