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 deoxynucleotidyltransferase, 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).
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. PMID2518659.
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. PMID3144456.
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.". Cell27 (3 Pt 2): 583–91. doi:10.1016/0092-8674(81)90400-1. PMID6101209.
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.". Nature300 (5894): 709–13. doi:10.1038/300709a0. PMID6817141.
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. PMID14702039.
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.". Blood103 (12): 4602–9. doi:10.1182/blood-2003-11-3857. PMID15010366.
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. PMID15191563.
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. PMID15607820.
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.". Leukemia19 (4): 652–8. doi:10.1038/sj.leu.2403644. PMID15703784.
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.". Leukemia19 (4): 659–63. doi:10.1038/sj.leu.2403661. PMID15716988.
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. Lymphoma46 (10): 1513–6. doi:10.1080/10428190500125648. PMID16194898.