Immunoglobulin Dimmunoglobulin deficiency, immunoglobulin definition
Immunoglobulin D IgD is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually coexpressed with another cell surface antibody called IgM IgD is also produced in a secreted form that is found in very small amounts in blood serum, representing 025% of immunoglobulins in serum Relative molecular mass and half-life of secreted IgD is 185 kDa and 28 days, respectively Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta δ class, and two Ig light chains
- 1 Function
- 2 Method of coexpression
- 3 References
- 4 External links
IgD's function has always been a puzzle in immunology since its discovery in 1964 IgD is 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 cells, IgD's function is to signal the B cells to be activated By being activated, B cells 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 A 2016 study by Übelhart and colleagues found that IgD signaling is only triggered by repetitive multivalent immunogens, while IgM can be triggered either by soluble monomeric or by multivalent immunogens 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 humans 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 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 introns in between them
Alternative 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 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 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
Zinc finger protein 318 ZNF318 has a role in the promotion of IgD expression and controlling the alternative splicing of the long pre-mRNA In immature B cells that mainly express the μ transcript, there is no ZFP318 expression, but in mature B cells with dual IgM and IgD expression, both δ and μ transcript is made and ZFP318 is expressed Enders et al 2014 found in mice that null mutations in ZFP318 resulted in no IgD expression
- ^ Rogentine GN, Rowe DS, Bradley J, Waldmann TA, Fahey JL 1966 "Metabolism of human immunoglobulin D IgD" PDF J Clin Invest 45 9: 1467–78 doi:101172/JCI105454 PMC 292826 PMID 5919348
- ^ Ohta, Yuko; Martin Flajnik 2006-07-11 "IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates" Proceedings of the National Academy of Sciences 103 28: 10723–10728 doi:101073/pnas0601407103 PMC 1636022 PMID 16818885 Retrieved 2009-10-02
- ^ Übelhart, R; Hug, E; Bach, MP; Wossning, T; Dühren-von Minden, M; Horn, AH; Tsiantoulas, D; Kometani, K; Kurosaki, T; Binder, CJ; Sticht, H; Nitschke, L; Reth, M; Jumaa, H "Responsiveness of B cells is regulated by the hinge region of IgD" Nat Immunol 16 5: 534–43 doi:101038/ni3141 PMID 25848865
- ^ Edholm ES, Bengten E, Wilson M 2011 "Insights into the function of IgD" Dev Comp Immunol 35 12: 1309–16 doi:101016/jdci201103002 PMID 21414345
- ^ Nitschke L, Kosco MH, Köhler G, Lamers MC 1993 "Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens" Proc Natl Acad Sci USA 90 5: 1887–91 doi:101073/pnas9051887 PMC 45985 PMID 8446604
- ^ Chen, Kang; Xu, Weifeng; Wilson, Melanie; He, Bing; Miller, Norman W; Bengtén, Eva; Edholm, Eva-Stina; Santini, Paul A; et al 2009 "Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell–stimulating programs in basophils" Nature Immunology 10 8: 889–898 doi:101038/ni1748 PMC 2785232 PMID 19561614
- ^ a b Murphy, K; Weaver, C 2016 Janeway's Immunobiology New York, NY: Garland Science/Taylor and Francis p 195 ISBN 9780815345053
- ^ Enders, A, Short, A, Miosge, L, Bergmann, H, Sontani, Y, Bertram, E, Whittle, B, Balakishnan, B, Yoshida, K, Sjollema, G, Field, M, Andrews, T, Hagiwara, H and Goodnow, C 2014 "Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes" Proceedings of the National Academy of Sciences 111 12: 4513–4518 doi:101073/pnas1402739111 PMC 3970522 PMID 24616512 CS1 maint: Uses authors parameter link
- Immunoglobulin+D at the US National Library of Medicine Medical Subject Headings MeSH
|see also disorders of globin and globulin proteins|
immunoglobulin d (igd), immunoglobulin d function, immunoglobulin deficiency, immunoglobulin deficiency in adults, immunoglobulin deficiency in children, immunoglobulin definition, immunoglobulin diagram, immunoglobulin disorder, immunoglobulin domains, immunoglobulin dosage
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