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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

IGH  -  immunoglobulin heavy locus

Homo sapiens

Synonyms: IGD1, IGH.1@, IGH@, IGHD@, IGHDY1, ...
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Disease relevance of IGH@


High impact information on IGH@

  • 2D-DE, as illustrated here for the IGH gene cluster, has general application in the development of large scale physical maps of gene and repeat families [6].
  • This analysis revealed that the human QIN gene maps to chromosome region 14q11.2-->14q32, between the TCR and IGH loci [7].
  • The degree of linkage disequilibrium measured between IGH polymorphic loci was then compared with the physical distance separating the loci [8].
  • Molecular cloning of the immunoglobulin heavy-chain locus (IGH) of this cell line revealed an unknown segment linked 5' to IGH [9].
  • In most eBL (13 out of 16) the breakpoints were mapped within or 5' to the IGH joining (JH region on chromosome 14 and outside the MYC locus on chromosome 8 [4].

Chemical compound and disease context of IGH@


Biological context of IGH@


Anatomical context of IGH@


Associations of IGH@ with chemical compounds

  • The immunoglobulin heavy chain (IGH) gene cluster and the gene coding for the brain form of the enzyme creatine kinase (CKB) have previously been localized to chromosome 14, at 14q32.3 and 14q32, respectively [18].
  • Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J(H), in the remaining case [19].

Physical interactions of IGH@

  • Sequence analysis showed that the genomic breakpoint is localized between the S(mu) region of the IGH complex and the first intron of BCL2 [13].

Enzymatic interactions of IGH@

  • Hybridization studies with various DNA probes from the IGH locus as well as the BCL2 gene demonstrated that the mu-constant gene was deleted on the functional IGH allele of FL-318G cells, and that the cells produced abundant productive gamma-chain messages [20].

Regulatory relationships of IGH@

  • This may be one possible mechanism of deregulating FOXP1 expression by placing it under the control of IGH enhancers [21].

Other interactions of IGH@

  • Translocations involving the MYC locus were detected in six cases, five of them derived from a MYC/IGH juxtaposition and one from a translocation involving a non-IG gene partner [1].
  • Rearrangements of the BCL6 locus were detected in five B-cell lymphomas of the leg, and involved IGH (two cases), IGL (one case), and non-IG genes (two cases) [1].
  • V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma [12].
  • Taken together these results support the hypothesis that enhanced BCL10 expression caused by translocation to the IGH locus can promote formation of MALT lymphomas [22].
  • The translocation brought the Sgamma2 region of a productive IGH allele 20 approximately 30 kbp upstream of FCGR2B [23].

Analytical, diagnostic and therapeutic context of IGH@

  • Sequence analysis of the V(H) region of the functional nontranslocated IGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center [13].
  • With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (S(mu)) region instead of the J(H) or D(H) gene segments was identified [13].
  • Genomic DNA extracted from tumor tissues was subjected to long-distance polymerase chain reaction (LD-PCR) using oligonucleotide primers for exon 2 of c-MYC and for the four constant region genes of IGH [14].
  • We studied the exact configuration of both the nontranslocated IGH allele and the MYC/IGH breakpoint by applying a combination of low- and high-resolution methods (interphase FISH, DNA fiber FISH, long-distance PCR, and Southern blotting) on 16 BL [24].
  • Molecular cloning of a 5'-BCL2/IGH junction demonstrated recombination of the two affected genes in divergent orientation [25].


  1. Molecular cytogenetic analysis of chromosomal breakpoints in the IGH, MYC, BCL6, and MALT1 gene loci in primary cutaneous B-cell lymphomas. Hallermann, C., Kaune, K.M., Gesk, S., Martin-Subero, J.I., Gunawan, B., Griesinger, F., Vermeer, M.H., Santucci, M., Pimpinelli, N., Willemze, R., Siebert, R., Neumann, C. J. Invest. Dermatol. (2004) [Pubmed]
  2. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Streubel, B., Vinatzer, U., Lamprecht, A., Raderer, M., Chott, A. Leukemia (2005) [Pubmed]
  3. Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative genomic hybridization. Berglund, M., Enblad, G., Flordal, E., Lui, W.O., Backlin, C., Thunberg, U., Sundström, C., Roos, G., Allander, S.V., Erlanson, M., Rosenquist, R., Larsson, C., Lagercrantz, S. Mod. Pathol. (2002) [Pubmed]
  4. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma. Neri, A., Barriga, F., Knowles, D.M., Magrath, I.T., Dalla-Favera, R. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  5. Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas. Baron, B.W., Nucifora, G., McCabe, N., Espinosa, R., Le Beau, M.M., McKeithan, T.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. The physical organization of the human immunoglobulin heavy chain gene complex. Walter, M.A., Surti, U., Hofker, M.H., Cox, D.W. EMBO J. (1990) [Pubmed]
  7. The human homologue of the retroviral oncogene qin maps to chromosome 14q13. Kastury, K., Li, J., Druck, T., Su, H., Vogt, P.K., Croce, C.M., Huebner, K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Nonuniform linkage disequilibrium within a 1,500-kb region of the human immunoglobulin heavy-chain complex. Walter, M.A., Cox, D.W. Am. J. Hum. Genet. (1991) [Pubmed]
  9. Molecular analysis of a chromosomal translocation, t(9;14)(p13;q32), in a diffuse large-cell lymphoma cell line expressing the Ki-1 antigen. Ohno, H., Furukawa, T., Fukuhara, S., Zong, S.Q., Kamesaki, H., Shows, T.B., Le Beau, M.M., McKeithan, T.W., Kawakami, T., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  10. IGH V3-23*01 and its allele V3-23*03 differ in their capacity to form the canonical human antibody combining site specific for the capsular polysaccharide of Haemophilus influenzae type b. Liu, L., Lucas, A.H. Immunogenetics (2003) [Pubmed]
  11. Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas. Martín-Subero, J.I., Odero, M.D., Hernandez, R., Cigudosa, J.C., Agirre, X., Saez, B., Sanz-García, E., Ardanaz, M.T., Novo, F.J., Gascoyne, R.D., Calasanz, M.J., Siebert, R. Genes Chromosomes Cancer (2005) [Pubmed]
  12. V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma. Vaandrager, J.W., Schuuring, E., Philippo, K., Kluin, P.M. Blood (2000) [Pubmed]
  13. Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells. Fenton, J.A., Vaandrager, J.W., Aarts, W.M., Bende, R.J., Heering, K., van Dijk, M., Morgan, G., van Noesel, C.J., Schuuring, E., Kluin, P.M. Blood (2002) [Pubmed]
  14. Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene. Akasaka, T., Akasaka, H., Ueda, C., Yonetani, N., Maesako, Y., Shimizu, A., Yamabe, H., Fukuhara, S., Uchiyama, T., Ohno, H. J. Clin. Oncol. (2000) [Pubmed]
  15. Frequency of chromosomal aneuploidies and deletions of the RB and TP53 genes in MALT lymphomas harboring the t(14;18)(q32;q21). Penas, E.M., Hinz, K., Biller, L., Zivkovic, T., Röser, K., Löning, T., Parwaresch, R., Bokemeyer, C., Dierlamm, J. Cancer Genet. Cytogenet. (2006) [Pubmed]
  16. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Streubel, B., Lamprecht, A., Dierlamm, J., Cerroni, L., Stolte, M., Ott, G., Raderer, M., Chott, A. Blood (2003) [Pubmed]
  17. High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies. Avet-Loiseau, H., Li, J.Y., Facon, T., Brigaudeau, C., Morineau, N., Maloisel, F., Rapp, M.J., Talmant, P., Trimoreau, F., Jaccard, A., Harousseau, J.L., Bataille, R. Cancer Res. (1998) [Pubmed]
  18. Localization and genetic linkage of the human immunoglobulin heavy chain genes and the creatine kinase brain (CKB) gene: identification of a hot spot for recombination. Benger, J.C., Teshima, I., Walter, M.A., Brubacher, M.G., Daouk, G.H., Cox, D.W. Genomics (1991) [Pubmed]
  19. Immunoglobulin V(H) somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome. Lai, R., Lefresne, S.V., Franko, B., Hui, D., Mirza, I., Mansoor, A., Amin, H.M., Ma, Y. Mod. Pathol. (2006) [Pubmed]
  20. Immunoglobulin heavy chain class switching, mu to gamma, in a human lymphoma cell line FL-318 carrying a t(14;18)(q32;q21) chromosomal translocation. Kadowaki, N., Amakawa, R., Hayashi, T., Akasaka, T., Yabumoto, K., Ohno, H., Fukuhara, S., Okuma, M. Leukemia (1995) [Pubmed]
  21. t(3;14)(p14;q32) results in aberrant expression of FOXP1 in a case of diffuse large B-cell lymphoma. Fenton, J.A., Schuuring, E., Barrans, S.L., Banham, A.H., Rollinson, S.J., Morgan, G.J., Jack, A.S., van Krieken, J.H., Kluin, P.M. Genes Chromosomes Cancer (2006) [Pubmed]
  22. Bcl10 can promote survival of antigen-stimulated B lymphocytes. Tian, M.T., Gonzalez, G., Scheer, B., DeFranco, A.L. Blood (2005) [Pubmed]
  23. Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas. Chen, W., Palanisamy, N., Schmidt, H., Teruya-Feldstein, J., Jhanwar, S.C., Zelenetz, A.D., Houldsworth, J., Chaganti, R.S. Oncogene (2001) [Pubmed]
  24. IGH switch breakpoints in Burkitt lymphoma: exclusive involvement of noncanonical class switch recombination. Guikema, J.E., de Boer, C., Haralambieva, E., Smit, L.A., van Noesel, C.J., Schuuring, E., Kluin, P.M. Genes Chromosomes Cancer (2006) [Pubmed]
  25. Rearrangement of the 5' cluster region of the BCL2 gene in lymphoid neoplasm: a summary of nine cases. Yabumoto, K., Akasaka, T., Muramatsu, M., Kadowaki, N., Hayashi, T., Ohno, H., Fukuhara, S., Okuma, M. Leukemia (1996) [Pubmed]
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