Skip to main content
Log in

Physical location of the human immunoglobulin lambda-like genes, 14.1, 16.1, and 16.2

  • Original Articles
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The human immunoglobulin lambda-like (IGLL) genes, which are homologous to the human immunoglobulin lambda (IGL) light chain genes, are expressed only in pre-B cells and are involved in B cell development. Three IGLL genes, 14.1, 16.1, and 16.2 are present in humans as opposed to one, λ5 (Igll), found in the mouse. To precisely map the location of the human IGLL genes in relation to each other and to the human IGL gene locus, at 22q11.1–2, a somatic cell hybrid panel and pulsed field gel electrophoresis (PFGE) were used. Hybridization with a λ-like gene-specific DNA probe to somatic cell hybrids revealed that these genes reside on 22q11.2 between the breakpoint cluster region (BCR) and the Ewing sarcoma breakpoint at 22q12 and that gene 16.1 was located distal to genes 14.1 and 16.2. Gene 14.1 was found by PFGE to be proximal to 16.2 by at least 30 kilobases (kb). A 210 kb Not I fragment containing genes 14.1 and 16.2 is adjacent to a 400 kb Not I fragment containing the BCR locus, which is just distal to the IGL-C (IGL constant region) genes. We have determined that the IGLL genes 14.1 and 16.2 are approximately 670 kb and 690 to 830 kb distal, respectively, to the 3′-most IGL-C gene in the IGL gene locus, IGL-C7. We thus show the first physical linkage of the IGL and the IGLL genes, 14.1 and 16.2. We discuss the relevance of methylation patterns and CpG islands to expression, and the evolutionary significance of the IGLL gene duplications. Consistent with the GenBank nomenclature, these human IGLL genes will be referred to as IGLL1 (14.1), IGLL2 (16.2), and IGLL3 (16.1), reflecting their position on chromosome 22, as established by this report.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arp, B., McMullen, M., and Storb, U. Sequences of immunoglobulin λ1 genes s in a λ1 defective mouse strain. Nature 298: 184–187, 1982

    Google Scholar 

  • Bauer, S. R., Huebner, K., Budarf, M., Finan, J., Erikson, J., Emanuel, B. S., Nowell, P. C., Croce, C. M., and Melchers, F. The human V pre B gene is located on chromosome 22 near a cluster of Vλ1 gene segments. Immunogenetics 28: 328–333, 1988

    Google Scholar 

  • Bauer, Jr., T. R. and Blomberg, B. A new λ-like light chain gene, 16.2, is related to genes 14.1 and 16.1 expressed in pre-B cells. J Cell Biochem Suppl 14D: 215 (M202), 1990

    Google Scholar 

  • Bauer, Jr., T. R. and Blomberg, B. The human λ L chain Ig locus: Recharacterization of JCλ6 and identification of a functional JCλ7. J Immunol 146: 2813–2820, 1991

    Google Scholar 

  • Bernard, P., Hozumi, N., and Tonegawa, S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell 15: 1135–1144, 1978

    Google Scholar 

  • Blomberg, B., Traunecker, A., Eisen, H., and Tonegawa, S. Organization of four mouse λ light chain immunoglobulin genes. Proc Natl Acad Sci USA 78: 3765–3769, 1981

    Google Scholar 

  • Blomberg, B. and Tonegawa, S. DNA sequences of the joining regions of mouse λ light chain immunoglobulin genes. Proc Natl Acad Sci USA 79: 530–533, 1982

    Google Scholar 

  • Blomberg, B. B., Rudin, C. M., and Storb, U. Identification and localization of an enhancer for the human λL chain Ig gene complex. J Immunol 147: 2354–2358, 1991

    Google Scholar 

  • Bossy, D., Milili, M. Zucman, J., Thomas, G., Fougereau, M., and Schiff, C. Organization and expression of the λ-like genes that contribute to the μ-Ψ light chain complex in human pre-B cells, Int Immunol 3: 1081–1090, 1991

    Google Scholar 

  • Budarf, M., Sellinger, B., Griffin, C., and Emanuel, B. S. Comparative mapping of the constitutional and tumor-associated 11;22 translocations. Am J Hum Genet 45: 128–139, 1989

    Google Scholar 

  • Caspersson, T., Gahrton, G., Lindsten, J., and Zech, L. Identification of the Philadelphia chromosome as a number 22 by quinacrine mustard fluorescence analysis. Exp Cell Res 63: 238–240, 1970

    Google Scholar 

  • Chang, H., Dmitrovsky, E., Hieter, P. A., Mitchell, K., Leder, P., Turoczi, L., Kirsch, I. R., and Hollis, G. F. Identification of three new Ig λ-like genes in man. J Exp Med 163: 425–435, 1986

    Google Scholar 

  • Combriato, G. and Klobeck, H.-G. Vλ and Jλ-Cλ gene segments of the human immunoglobulin λ light chain locus are separated by 14 kb and rearrange by a deletion mechanism. Eur J Immunol 21: 1513–1522, 1991

    Google Scholar 

  • Croce, C. M., Huebner, K., Isobe, M., Fainstain, E., Lifshitz, B., Shtivelman, E., and Canaani, E. Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints. Proc Natl Acad Sci USA 84: 7174–7178, 1987

    Google Scholar 

  • De la Chapelle, A., Herva, R., Koivisto, M., and Aula, P. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet 57: 253–256, 1981

    Google Scholar 

  • De la Chapelle, A., Lenoir, G., Boué, J., Boué, A., Gallano, P., Huerre, C., Szajnert, M.-F., Jeanpierre, M., Lalouel, J.-M., and Kaplan, J.-C. Lambda Ig constant region genes are translocated to chromosome 8 in Burkitt's lymphoma with t(8;22). Nucleic Acids Res 11: 1133–1142, 1983

    Google Scholar 

  • Delattre, O., Azambuja, C. J., Aurias, A., Zucman, J., Peter, M., Zhang, F., Hors-Cayla, M. C., Rouleau, G., and Thomas, G. Mapping of human chromosome 22 with a panel of somatic cell hybrids. Genomics 9: 721–727, 1991

    Google Scholar 

  • Diekmann, D., Brill, S., Garrett, M. D., Totty, N., Hsuan, J., Monfries, C., Hall, C., Lim, L., and Hall, A. BCR encodes a GTPase-activating protein for p21rac. Nature 351: 400–402, 1991

    Google Scholar 

  • Dumanski, J. P., Carlbom, E., Collins, V. P., and Nordenskjöld, M. Deletion mapping of locus on human chromosome 22 involved in the oncogenesis of meningioma. Proc Natl Acad Sci USA 84: 9275–9279, 1987

    Google Scholar 

  • Emanuel, B. S., Nowell, P. C., McKeon, C., Croce, C. M., and Israel, M. A. Translocation breakpoint mapping: molecular and cytogenetic studies of chromosome 22. Cancer Genet Cytogenet 19: 81–92, 1986

    Google Scholar 

  • Erikson, J., Martinis, J., and Croce, C. M. Assignment of the genes for human λ immunoglobulin to chromosome 22. Nature 294: 173–175, 1981

    Google Scholar 

  • Feinberg, A. P. and Vogelstein, B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132: 6–13, 1983

    Google Scholar 

  • Goyns, M. H., Young, B. D., Geurts van Kessel, A., de Klein, A., Grosveld, G., Bartram, C. R., and Bootsman, D. Regional mapping of the human immunoglobulin lambda light chain to the Philadelphia chromosome in chronic myeloid leukaemia. Leuk Res 8: 547–553, 1984

    Google Scholar 

  • Gugliemi, P. and Davi, F. Expression of a novel type of immunoglobulin Cλ transcripts in human mature B lymphocytes producing к light chains. Eur J Immunol 21: 501–508, 1991

    Google Scholar 

  • Hayzer, D. J. Immunoglobulin lambda light chain evolution: Ig1 and Ig1-like sequences form three major groups. Immunogenetics 32: 157–174, 1990

    Google Scholar 

  • Heisterkamp, N., Stam, K., Groffen, J., de Klein, A., and Grosveld, G. Structural organization of the bcr gene and its role in the Ph' translocation. Nature 315: 758–761, 1985

    Google Scholar 

  • Hieter, P. A., Hollis, G. F., Korsmeyer, S. J., Waldmann, T. A., and Leder, P. Clustered arrangement of immunoglobulin λ constant region genes in man. Nature 294: 536–540, 1981

    Google Scholar 

  • Hollis, G. F., Hieter, P. A., McBride, O. W., Swan, D., and Leder, P. Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA-type processing. Nature 296: 321–325, 1982

    Google Scholar 

  • Hollis, G. F., Evans, R. J., Stafford-Hollis, J. M., Korsmeyer, S. J., and McKearn, J. P. Immunoglobulin λ light-chain-related genes 14.1 and 16.1 are expressed in pre-B cells and may encode the human immunoglobulin ω light-chain protein. Proc Natl Acad Sci USA 86: 5552–5556, 1989

    Google Scholar 

  • Knight, J., Laing, P., Knight, A., Adams, D., and Ling, N. Thyroid-stimulating autoantibodies usually contain only λ-light chains: evidence for the “forbidden clone” theory. J Clin Endocrinol Metab 62: 342–347, 1986

    Google Scholar 

  • Kudo, A., Bauer, S., and Melchers, F. Structure, control of expression and putative function of the preB cell-specific genes VpreB and λ5. In F. Melchers, E. D. Albert, H. von Boehmer, M. P. Dierich, L. Du Pasquier, K. Eichmann, D. Gemsa, O. Götze, J. R. Kalden, S. H. E. Kaufmann, H. Kirchner, K. Resch, G. Riethmüller, A. Schimpl, C. Sorg, M. Steinmetz, H. Wagner, and H. G. Zachau (eds): Progress in Immunology, pp. 339–347, Springer, Berlin Heidelberg New York, 1989

    Google Scholar 

  • Kudo, A. and Melchers, F. A second gene, VpreB in the λ5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J 6: 2267–2272, 1987

    Google Scholar 

  • Kudo, A., Pravtcheva, D., Sakaguchi, N., Ruddle, F. H., and Melchers, F. Localization of the murine λ5 gene on chromosome 16. Genomics 1: 277–279, 1987a

    Google Scholar 

  • Kudo, A., Sakaguchi, N., and Melchers, F. Organization of the murine-Ig-related λ5 gene transcribed selectively in pre-B lymphocytes. EMBO J 6: 103–107, 1987; Corrigendum: EMBO J 6: 4242, 1987b

    Google Scholar 

  • Larsen, F., Gundersen, G., Lopez, R., and Prydz, H. CpG islands as gene markers in the human genome. Genomics 13: 1095–1107, 1992

    Google Scholar 

  • Ledbetter, S. A., Garcia-Heras, J., and Ledbetter, D. H. “PCR-karyo-type” of human chromosomes in somatic cell hybrids. Genomics 8: 614–622, 1990

    Google Scholar 

  • Lindsay, S. and Bird, A. P. Use of restriction enzymes to detect potential gene sequences in mammalian DNA. Nature 327: 336–338, 1987

    Google Scholar 

  • Mattei, M.-G., Fumoux, F., Roeckel, N., Fougereau, M., and Schiff, C. The human pre-B-specific λ-like cluster is located in the 22q11.2–22q12.3 region, distal to the IgCλ locus. Genomics 9: 544–546, 1991

    Google Scholar 

  • McBride, O. W., Hieter, P. A., Hollis, G. F., Swan, D., Otey, M. C., and Leder, P. Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes. J Exp Med 155: 1480–1490, 1982

    Google Scholar 

  • McDermid, H. E., Duncan, A. M. V., Brasch, K. P., Holden, J. J. A., Magenis, E., Sheehy, R., Burn, J., Kardon, N., Noel, B., Schinzel, A., Teshima, I., and White, B. N. Characterization of the supernumerary chromosome in Cat Eye syndrome. Science 232: 646–648, 1986

    Google Scholar 

  • McDermid, H. E., Budarf, M. L., and Emanuel, B. S. Toward a long-range map of human chromosome band 22q11. Genomics 5: 1–8, 1989

    Google Scholar 

  • McDermid, H. E., Budarf, M. L., and Emanuel, B. S. Long-range restriction map of human chromosome 22q11–22q12 between the lambda immunoglobulin locus and the Ewing sarcoma breakpoint. Genomics, in press, 1993

  • Poul, M.-A., Zhang, X.-M., Ducret, F., and Lefranc, M. P. The IGLJ6 joining segment as a STS in the human immunoglobulin lambda light chain constant region gene locus (located at 22q11). Nucleic Acids Res 19: 4785, 1991

    Google Scholar 

  • Rouleau, G. A., Wertelecki, W., Haines, J. L., Hobbs, W. J., Trofatter, J. A., Seizinger, B. R., martuza, R. L., Superneau, D. W., Conneally, P. M., and Gusella, J. F. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 329: 246–248, 1987

    Google Scholar 

  • Sakaguchi, N. and Melchers, F. λ5, a new light-chain-related locus selectively expressed in pre-B lymphocytes. Nature 324: 579–582, 1986

    Google Scholar 

  • Schiff, C., Milili, M., and Fourgereau, M. Isolation of early immunoglobulin λ-like gene transcripts in human fetal liver. Eur J Immunol 19: 1873–1878, 1989

    Google Scholar 

  • Schiff, C., Bensmana, M., Guglielmi, P., Milili, M., Lefranc, M.-P., and Fougereau, M. The immunoglobulin λ-like gene cluster (14.1, 16.1, and Fλ1) contains gene(s) selectively expressed in pre-B cells and is the human counterpart of the mouse λ5 gene. Int Immunol 2: 201–207, 1990

    Google Scholar 

  • Selsing, E., Miller, J., Wilson, R., and Storb, U. Evolution of mouse immunoglobulin λ genes. Proc Natl Acad Sci USA 79: 4681–4685, 1982

    Google Scholar 

  • Shtivelman, E., Lifshitz, B., Gale, R. P., and Canaani, E. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 315: 550–554, 1985

    Google Scholar 

  • Smith, C. L., Klco, S. R., and Cantor, C. R. Pulsed field gel electrophoresis and the technology of large DNA molecules. In K. E. Davies (ed.): Genome Analysis: A Practical Approach, pp. 41–60, IRL press, Washington, DC, 1988

    Google Scholar 

  • Southern, E. M. Detection of specific sequences among DNA fr separated by gel electrophoresis. J Mol Biol 98: 503–517, 1975

    Google Scholar 

  • Stewart, G. D., Tanzi, R. E., Kishimoto, T. K., Buraczynska, M., Haines, J. L., Drabkin, H., Gusella, J. F., Springer, T. A., Kurnit, D. M., and Van Keuren, M. The CD18 gene maps to distal chromosome 21q22.3: RFLPs create a highly informative terminal haplotype. Am J Hum Genet 43: 3 (Suppl A160), 1988

  • Storb, U. and Arp, B. Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation. Proc Natl Acad Sci USA 80: 6642–6646, 1983

    Google Scholar 

  • Storb, U., Haasch, D., Arp, B., Sanchez, P., Cazenave, P.-A., and Miller, J. Physical linkage of mouse λ genes by pulsed field gel electrophoresis suggests that the rearrangement process favors proximate target sequences. Mol Cell Biol 9: 711–718, 1989

    Google Scholar 

  • Tsujimoto, Y. and Croce, C. M. Molecular cloning of human immunoglobulin λ chain variable sequence. Nucleic Acids Res 12: 8407–8414, 1984

    Google Scholar 

  • Udey, J. A. and Blomberg, B. Human λ light chain locus: organization and DNA sequences of three genomic J regions. Immunogenetics 25: 63–70, 1987

    Google Scholar 

  • Udey, J. A. and Blomberg, B. B. Intergenic exchange maintains identity between two human lambda light chain immunoglobulin gene intron sequences. Nucleic Acids Res 16: 2959–2969, 1988

    Google Scholar 

  • Vasicek, T. J. and Leder, P. Structure and expression of the human immunoglobulin λ genes. J Exp Med 172: 609–620, 1990

    Google Scholar 

  • Zakarija, M. Immunochemical characterization of the thyroid-stimulating antibody (TSAb) of Graves' disease: evidence for restricted heterogeneity. J Clin Lab Immunol 10: 77–85, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: B. B. Blomberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bauer, T.R., McDermid, H.E., Budarf, M.L. et al. Physical location of the human immunoglobulin lambda-like genes, 14.1, 16.1, and 16.2 . Immunogenetics 38, 387–399 (1993). https://doi.org/10.1007/BF00184519

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00184519

Keywords

Navigation