IGH@

IGH
Identifiers
Aliases	IGH , IGD1, IGH.1@, IGH@, IGHD@, IGHDY1, IGHJ, IGHJ@, IGHV, IGHV@, immunoglobulin heavy locus, IgH locus
External IDs	OMIM: 146910, 147010, 147070 GeneCards: IGH
Orthologs
	3492
	n/a
	n/a
	n/a
	n ; a
	n/a
	n/a
	n/a
	n/a
	n/a
	Wikidata
View/Edit Human

Last updated October 15, 2022

Immunoglobulin heavy locus, also known as IGH, is a region on human chromosome 14 that contains a gene for the heavy chains of human antibodies (or immunoglobulins).^[2]

Immunoglobulins recognize foreign antigens and initiate immune responses such as phagocytosis and the complement system. Each immunoglobulin molecule consists of two identical heavy chains and two identical light chains. This region represents the germline organization of the heavy chain locus. The locus includes V (variable), D (diversity), J (joining), and C (constant) segments. During B cell development, a recombination event at the DNA level joins a single D segment with a J segment; the fused D-J exon of this partially rearranged D-J region is then joined to a V segment. The rearranged V-D-J region containing a fused V-D-J exon is then transcribed and fused at the RNA level to the IGHM constant region; this transcript encodes a mu heavy chain. Later in development B cells generate V-D-J-Cmu-Cdelta pre-messenger RNA, which is alternatively spliced to encode either a mu or a delta heavy chain. Mature B cells in the lymph nodes undergo switch recombination, so that the fused V-D-J gene segment is brought in proximity to one of the IGHG, IGHA, or IGHE gene segments and each cell expresses either the gamma, alpha, or epsilon heavy chain. Potential recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random addition of nucleotides by terminal deoxynucleotidyl transferase, and by somatic hypermutation, which occurs during B cell maturation in the spleen and lymph nodes. Several V, D, J, and C segments are known to be incapable of encoding a protein and are considered pseudogenous gene segments (often simply referred to as pseudogenes).^[2]

Nomenclature

Symbols for variable (V) immunoglobulin gene segments start with IGHV and include two or three numbers separated by dashes. Examples:

IGHV1-2, IGHV1-3, …, IGHV1-69-2, IGHV2-5, …, IGHV7-4-1

Symbols for diversity (D) immunoglobulin gene segments start with IGHD and include two numbers separated by dashes. Examples:

IGHD1-1, IGHD1-7, …, IGHD7-27

Symbols for joining (J) immunoglobulin gene segments:

IGHJ1, IGHJ2, IGHJ3, IGHJ4, IGHJ5, IGHJ6

Symbols for constant region (C) immunoglobulin genes:

Heavy chain alpha (IgA): IGHA1, IGHA2

Heavy chain gamma (IgG): IGHG1, IGHG2, IGHG3, IGHG4

Heavy chain delta (IgD): IGHD

Heavy chain epsilon (IgE): IGHE

Heavy chain mu (IgM): IGHM ^[3]

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Immunoglobulin D</span>

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 co-expressed 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 0.25% of immunoglobulins in serum. The relative molecular mass and half-life of secreted IgD is 185 kDa and 2.8 days, respectively. Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta (δ) class, and two Ig light chains.

Immunoglobulin M (IgM) is one of several isotypes of antibody that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen. In humans and other mammals that have been studied, plasmablasts residing in the spleen are the main source for specific IgM production.

Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the AICDA gene. It creates mutations in DNA by deamination of cytosine base, which turns it into uracil. In other words, it changes a C:G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a T:A base pair. During germinal center development of B lymphocytes, AID also generates other types of mutations, such as C:G to A:T. The mechanism by which these other mutations are created is not well understood. It is a member of the APOBEC family.

<span class="mw-page-title-main">Immunoglobulin heavy chain</span> Large polypeptide subunit of an antibody

The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of an antibody (immunoglobulin). In human genome, the IgH gene loci are on chromosome 14.

V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.

Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each mature B lymphocyte to express only one type of immunoglobulin. This subsequently results in each B lymphocyte being able to recognize only one antigen. This is significant as the co-expression of both alleles in B lymphocytes is associated with autoimmunity and the production of autoantibodies.

Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG. During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.

<span class="mw-page-title-main">Immunoglobulin light chain</span> Small antibody polypeptide subunit (immunoglobin)

The immunoglobulin light chain is the small polypeptide subunit of an antibody (immunoglobulin).

Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the IRF4 gene, located at 6p25-p23. IRF4 functions as a key regulatory transcription factor in the development of human immune cells. The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells.

Immunoglobulin lambda-like polypeptide 1 is a protein that in humans is encoded by the IGLL1 gene. IGLL1 has also recently been designated CD179B.

<span class="mw-page-title-main">IGHM</span> Gene in the species Homo sapiens

Ig mu chain C region is a protein that in humans is encoded by the IGHM gene.

Ig delta chain C region is a protein that in humans is encoded by the IGHD gene.

Immunoglobulin lambda locus, also known as IGL@, is a region on the q arm of human chromosome 22, region 11.22 (22q11.22) that contains genes for the lambda light chains of antibodies.

Immunoglobulin iota chain is a protein that in humans is encoded by the VPREB1 gene. VPREB1 has also recently been designated CD179A.

Ig heavy chain V-III region VH26 is a protein that in humans is encoded by the IGHV@ gene.

Ig gamma-3 chain C region is a protein that in humans is encoded by the IGHG3 gene.

Ig gamma-4 chain C region is a protein that in humans is encoded by the IGHG4 gene.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Antibody structure is made up of two heavy-chains and two light-chains. These chains are held together by disulfide bonds. The arrangement or processes that put together different parts of this antibody molecule play important role in antibody diversity and production of different subclasses or classes of antibodies. The organization and processes take place during the development and differentiation of B cells. That is, the controlled gene expression during transcription and translation coupled with the rearrangements of immunoglobulin gene segments result in the generation of antibody repertoire during development and maturation of B cells.

References

↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: IGH immunoglobulin heavy locus".
↑ "Gene Family: Immunoglobulin heavy locus at 14q32.33 (IGH)". HGNC: HUGO Gene Nomenclature Committee.

Tomlinson IM, Cook GP, Walter G, et al. (1995). "A complete map of the human immunoglobulin VH locus". Ann. N. Y. Acad. Sci. 764 (1): 43–6. Bibcode:1995NYASA.764...43T. doi:10.1111/j.1749-6632.1995.tb55804.x. PMID 7486559. S2CID 43106266.
Word CJ, White MB, Kuziel WA, et al. (1991). "The human immunoglobulin C mu-C delta locus: complete nucleotide sequence and structural analysis". Int. Immunol. 1 (3): 296–309. doi:10.1093/intimm/1.3.296. PMID 2518659.
Buluwela L, Rabbitts TH (1989). "A VH gene is located within 95 Kb of the human immunoglobulin heavy chain constant region genes". Eur. J. Immunol. 18 (11): 1843–5. doi:10.1002/eji.1830181130. PMID 3144456. S2CID 21128167.
Ichihara Y, Matsuoka H, Kurosawa Y (1989). "Organization of human immunoglobulin heavy chain diversity gene loci". EMBO J. 7 (13): 4141–50. doi:10.1002/j.1460-2075.1988.tb03309.x. PMC 455124 . PMID 3243276.
Ravetch JV, Siebenlist U, Korsmeyer S, et al. (1993). "Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes". Cell. 27 (3 Pt 2): 583–91. doi:10.1016/0092-8674(81)90400-1. PMID 6101209. S2CID 20229287.
Flanagan JG, Rabbitts TH (1983). "Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes". Nature. 300 (5894): 709–13. doi:10.1038/300709a0. PMID 6817141. S2CID 4335031.
Mills FC, Harindranath N, Mitchell M, Max EE (1997). "Enhancer complexes located downstream of both human immunoglobulin Calpha genes". J. Exp. Med. 186 (6): 845–58. doi:10.1084/jem.186.6.845. PMC 2199054 . PMID 9294139.
Matsuda F, Ishii K, Bourvagnet P, et al. (1999). "The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus". J. Exp. Med. 188 (11): 2151–62. doi:10.1084/jem.188.11.2151. PMC 2212390 . PMID 9841928.
Dudley DD, Manis JP, Zarrin AA, et al. (2002). "Internal IgH class switch region deletions are position-independent and enhanced by AID expression". Proc. Natl. Acad. Sci. U.S.A. 99 (15): 9984–9. Bibcode:2002PNAS...99.9984D. doi: 10.1073/pnas.152333499 . PMC 126611 . PMID 12114543.
Zhou J, Ashouian N, Delepine M, et al. (2002). "The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13693–8. Bibcode:2002PNAS...9913693Z. doi: 10.1073/pnas.212392399 . PMC 129745 . PMID 12370427.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID 14702039.
Li A, Rue M, Zhou J, et al. (2004). "Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis". Blood. 103 (12): 4602–9. doi: 10.1182/blood-2003-11-3857 . PMID 15010366.
Hallermann C, Kaune KM, Gesk S, et al. (2004). "Molecular cytogenetic analysis of chromosomal breakpoints in the IGH, MYC, BCL6, and MALT1 gene loci in primary cutaneous B-cell lymphomas". J. Invest. Dermatol. 123 (1): 213–9. doi: 10.1111/j.0022-202X.2004.22720.x . PMID 15191563.
Sepulveda MA, Garrett FE, Price-Whelan A, Birshtein BK (2005). "Comparative analysis of human and mouse 3' Igh regulatory regions identifies distinctive structural features". Mol. Immunol. 42 (5): 605–15. doi:10.1016/j.molimm.2004.09.006. PMID 15607820.
Streubel B, Vinatzer U, Lamprecht A, et al. (2005). "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma". Leukemia. 19 (4): 652–8. doi: 10.1038/sj.leu.2403644 . PMID 15703784.
Knezevich S, Ludkovski O, Salski C, et al. (2005). "Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas". Leukemia. 19 (4): 659–63. doi: 10.1038/sj.leu.2403661 . PMID 15716988.
Rack K, Delannoy A, Ravoet C, et al. (2005). "Translocation of BCL2 and BCL6 to the same immunoglobulin heavy chain locus in a case of follicular lymphoma". Leuk. Lymphoma. 46 (10): 1513–6. doi:10.1080/10428190500125648. PMID 16194898. S2CID 10501344.

This protein-related article is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[1] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-2] 1 2 "Entrez Gene: IGH immunoglobulin heavy locus".

[3] "Gene Family: Immunoglobulin heavy locus at 14q32.33 (IGH)". HGNC: HUGO Gene Nomenclature Committee.

[1]

[2]

[3]

v t e Antibodies
Main types	IgA IgD IgE IgG IgM IgY
Chains	Light chain IGK@ IGL@ surrogate IGLL1 Heavy chain IGH@ IGHM Heavy-chain antibody/IgNAR

IGH@

Contents

Nomenclature

See also

Related Research Articles

References

Further reading