Immunoglobulin D
Encyclopedia
Immunoglobulin D is an antibody
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...

 isotype
Isotype (immunology)
An isotype usually refers to any related proteins/genes from a particular gene family. In immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains...

 that makes up about 1% of protein
Protein
Proteins 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...

s in the plasma membranes of immature B-lymphocytes where it is usually coexpressed with another cell surface antibody called IgM
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...

. IgD is also produced in a secreted form that is found in very small amounts in blood serum
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...

. Secreted IgD is produced as a monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

ic antibody with two heavy chain
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...

s of the delta (δ) class, and two Ig light chain
Light chain
A light chain is the small polypeptide subunit of a protein complex.More specifically, it can refer to:* Immunoglobulin light chain* Ferritin light chain* Myosin light chain* Kinesin light chain* Dynein light chainLight chain may also refer to:...

s.

Function

IgD's function has always been a puzzle in immunology since its discovery in 1964. IgD was recently found to be present in species from cartilaginous fish to human (probably with the exception of birds). This nearly ubiquitous appearance in species with an adaptive immune system demonstrates that IgD is as ancient as IgM and suggests the notion that IgD has important immunological functions.

In B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s, IgD's function is to signal the B cells to be activated. By being activated, they are ready to take part in the defense of the body in the immune system. During B-cell differentiation, IgM is the exclusive isotype expressed by immature B cells. IgD starts to be expressed when the B-cell exits the bone marrow to populate peripheral lymphoid tissues. When a B-cell reaches its mature state, it co-expresses both IgM and IgD. It is not well understood whether IgM and IgD antibodies are functionally different on B cells. Cδ Knockout mice (mice that have been genetically altered so that they do not produce IgD) have no major B-cell intrinsic defects. IgD may have some role in allergic reactions.

Recently, IgD was found to bind to basophils and mast cells and activate these cells to produce antimicrobial factors to participate in respiratory immune defense in human. It also stimulates basophils to release B-cell homeostatic factors. This is consistent with the reduction in the number of peripheral B cells, reduced serum IgE level and defective primary IgG1 response in IgD knockout mice.

Method of Coexpression

In the human Heavy-Chain Locus, 3' of the V-D-J cassette is a series of C (for constant) genes, each conferring to an Ig isotype.
The Cμ [IgM]gene is 3' and closest to the V-D-J cassette, with the Cδ gene appearing 3' to Cμ.

A Primary mRNA transcript will contain the transcribed V-D-J cassette, and the Cμ and Cδ genes, with intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...

s in between them.

Alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 can then occur, causing a selection of either Cμ or Cδ to appear on the functional mRNA (μ mRNA and δ mRNA respectively). Alternative splicing is thought to be possible due to two Polyadenylation
Polyadenylation
Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...

 sites, one appearing between the Cμ and Cδ, and the other 3' of Cδ (polyadenylation in the latter site would cause Cμ to be spliced away along with the intron). The precise mechanism of how the polyadenylation site is chosen remains unclear.

The resulting functional mRNA will have the V-D-J and C regions contiguous, and its translation
Translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. Whereas interpreting undoubtedly antedates writing, translation began only after the appearance of written literature; there exist partial translations of the Sumerian Epic of...

will generate either a μ heavy chain or δ heavy chain. the heavy chains then couple with either κ or λ light chains to create the final IgM or IgD antibody.
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