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; OMA:IGH - orthologs
Orthologs Species Human Mouse Entrez 3492 n/a Ensembl n/a n/a UniProt n a n/a RefSeq (mRNA) n/a n/a RefSeq (protein) n/a n/a Location (UCSC) n/a n/a PubMed search n/a
Wikidata
View/Edit Human

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).

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).

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

See also

• IGHV@

Further reading

• 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.