Biology:IGH@

Short description: Region on human chromosome 14

Generic protein structure example

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

• "A complete map of the human immunoglobulin VH locus.". Ann. N. Y. Acad. Sci. 764 (1): 43–6. 1995. doi:10.1111/j.1749-6632.1995.tb55804.x. PMID 7486559. Bibcode: 1995NYASA.764...43T. 
• "The human immunoglobulin C mu-C delta locus: complete nucleotide sequence and structural analysis.". Int. Immunol. 1 (3): 296–309. 1991. doi:10.1093/intimm/1.3.296. PMID 2518659. 
• "A VH gene is located within 95 Kb of the human immunoglobulin heavy chain constant region genes.". Eur. J. Immunol. 18 (11): 1843–5. 1989. doi:10.1002/eji.1830181130. PMID 3144456. 
• "Organization of human immunoglobulin heavy chain diversity gene loci.". EMBO J. 7 (13): 4141–50. 1989. doi:10.1002/j.1460-2075.1988.tb03309.x. PMID 3243276. 
• "Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.". Cell 27 (3 Pt 2): 583–91. 1993. doi:10.1016/0092-8674(81)90400-1. PMID 6101209. 
• "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. 1983. doi:10.1038/300709a0. PMID 6817141. 
• "Enhancer complexes located downstream of both human immunoglobulin Calpha genes.". J. Exp. Med. 186 (6): 845–58. 1997. doi:10.1084/jem.186.6.845. PMID 9294139. 
• "The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus.". J. Exp. Med. 188 (11): 2151–62. 1999. doi:10.1084/jem.188.11.2151. PMID 9841928. 
• "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. 2002. doi:10.1073/pnas.152333499. PMID 12114543. Bibcode: 2002PNAS...99.9984D. 
• "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. 2002. doi:10.1073/pnas.212392399. PMID 12370427. Bibcode: 2002PNAS...9913693Z. 
• "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039. 
• "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. 2004. doi:10.1182/blood-2003-11-3857. PMID 15010366. 
• "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. 2004. doi:10.1111/j.0022-202X.2004.22720.x. PMID 15191563. 
• "Comparative analysis of human and mouse 3' Igh regulatory regions identifies distinctive structural features.". Mol. Immunol. 42 (5): 605–15. 2005. doi:10.1016/j.molimm.2004.09.006. PMID 15607820. 
• "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma.". Leukemia 19 (4): 652–8. 2005. doi:10.1038/sj.leu.2403644. PMID 15703784. 
• "Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas.". Leukemia 19 (4): 659–63. 2005. doi:10.1038/sj.leu.2403661. PMID 15716988. 
• "Translocation of BCL2 and BCL6 to the same immunoglobulin heavy chain locus in a case of follicular lymphoma.". Leuk. Lymphoma 46 (10): 1513–6. 2005. doi:10.1080/10428190500125648. PMID 16194898.