Skip to main content
Log in

Gene segments encoding membrane domains of the human immunoglobulin gamma 3 and alpha chains

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

Abstract

The carboxyterminal region of the heavy chains, according to its hydrophilic or hydrophobic properties, determines whether the immunoglobulin will be secreted or membrane-bound. We have determined the nucleotide sequences of the human IGHG3, IGHA1, and IGHA2 membrane exons isolated from genomic DNA libraries. The IGHG3 M1 and M2 exons are separated by a long intron of 2.1 kilobases (kb) containing an highly repeated motif of 34 base pairs (bp). The IGHA1 and IGHA2 genes, like the mouse Igh-A gene, have a single exon encoding the extracellular, transmembrane, and cytoplasmic regions. For each class of immunoglobulins, the sequences of membrane exons are highly conserved between human and mouse, but no alignment is possible for the flanking regions. In contrast, for a same species, the sequences of the heavy chain membrane exons differ from one class to another. While the hydrophobic profile of the membrane core is well conserved, the cytoplasmic region differs in length and in composition. None of the intracellular domains presents the sequence implied in signal transduction, implying that membrane immunoglobulins need other proteins, which probably interact with the constant or membrane domain, to transmit signals leading to B-cell activation.

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

  • Alt, F. W., Bothwell, A. L. M., Knapp, M., Siden, E., Mather, E., Koshland, M., and Baltimore, D.: Synthesis of secreted and membrane-bound immunoglobulin Mu heavy chains is directed by mRNAs that differ at their 3′ ends. Cell 20: 293–301, 1980

    Google Scholar 

  • Bensmana, M., Huck, S., Lefranc, G., and Lefranc, M.-P.: The human immunoglobulin pseudo-gamma IGHGP gene shows no major structural defect. Nucleic Acids Res 16: 3108, 1988

    Google Scholar 

  • Breathnach, R., Benoist, C., O'Hare, K., Gannon, F., and Chambon, P.: Ovalbumin gene: evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries. Proc Natl Acad Sci USA 75: 4853–4857, 1978

    Google Scholar 

  • Cambier, J. C. and Ransom, J. T.: Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol 5: 175–199, 1987

    Google Scholar 

  • Campbell, K. S. and Cambier, J. C.: B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex. EMBO J 9: 441–448, 1990

    Google Scholar 

  • Chen, Z. Z., Coggeshall, K. M., and Cambier, J. C.: Translocation of protein kinase C during membrane immunoglobulin mediated transmembrane signaling in B lymphocytes. J Immunol 136: 2300–2306, 1986

    Google Scholar 

  • Cheng, H.-L., Blattner, F. R., Fitzmaurice, L., Mushinski, J. F., and Tucker, P. W.: Structure of genes for membrane and secreted murine IgD heavy chains. Nature 296: 410–415, 1982

    CAS  PubMed  Google Scholar 

  • Clevers, H., Alarcon, B., Wileman, T., and Terhorst, C.: The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol 6: 629–662, 1988

    Google Scholar 

  • Croce, C. M., Shander, M., Martinis, J., Cicurel, M., D'amona, G. G., Dolby, T. W., and Koprowski, H.: Chromosomal location of the genes for human immunoglobulin heavy chains. Proc Natl Acad Sci USA 76: 3416–3419, 1979

    Google Scholar 

  • Dorai, H. and Gillies, S. D.: The complete nucleotide sequence of a human immunoglobulin genomic Cmu gene. Nucleic Acids Res 17: 15, 1989

    Google Scholar 

  • Early, P., Rogers, J., Davis, M., Calame, K., Bond, M., Wall, R., and Hood, L. E.: Two mRNA can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell 20: 313–319, 1980

    Google Scholar 

  • Ellison, J. W. and Hood, L. E.: Linkage and sequence homology of two human immunoglobulin gamma heavy-chain constant region genes. Proc Natl Acad Sci USA 79: 1984–1988, 1982

    Google Scholar 

  • Ellison, J. W., Buxbaum, J., and Hood, L. E.: Nucleotide sequence of a human immunoglobulin Cgamma4 gene. DNA 1: 11–18, 1981

    Google Scholar 

  • Ellison, J. W., Berson, B. J., and Hood, L. E.: The nucleotide sequence of a human immunoglobulin Cgamma1 gene. Nucleic Acids Res 10: 4071–4079, 1982

    Google Scholar 

  • Flanagan, J. G. and Rabbitts, T. H.: Arrangement of human immunoglobulin eplison heavy chain constant region genes implies evolutionary duplication of a segment containing γ, ε and α genes. Nature 300: 709–713, 1982a

    Google Scholar 

  • Flanagan, J. G. and Rabbitts, T. H.: The sequence of human immunoglobulin eplison heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J 1: 655–660, 1982b

    Google Scholar 

  • Flanagan, J. G., Lefranc, M.-P., and Rabbitts, T. H.: Mechanisms of divergence and convergence of the human immunoglobulin alpha1 and alpha2 constant region gene sequences. Cell 36: 681–688, 1984

    Article  CAS  PubMed  Google Scholar 

  • Ghanem, N., Dugoujon, J. F., Bensmana, M., Huck, S., Lefranc, M.-P., and Lefranc, G.: Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism. Eur J Immunol 18: 1067–1072, 1988a

    Google Scholar 

  • Ghanem, N., Lefranc, M.-P., and Lefranc, G.: Definition of the RFLP alleles in the human immunoglobulin IGHG gene locus. Eur J Immunol 18: 1059–1065, 1988b

    Google Scholar 

  • Guo, L. H., Yang, R. C. A., and Wu, R.: An improved strategy for rapid direct sequencing of both strands of long DNA molecules cloned in a plasmid. Nucleic Acids Res 11: 5521–5540, 1983

    Google Scholar 

  • Hammarström, L., Granem, N., Smith, C. I. E., Lefranc, G., and Lefranc, M.-P.: RFLP of human immunoglobulin genes. Exp Clin Immunogenet 7: 7–19, 1990

    Google Scholar 

  • Hombach, J., Leclercq, L., Radbruch, A., Rajewsky, K., and Reth, M.: A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells. EMBO J 7: 3451–3456, 1988

    Google Scholar 

  • Hombach, J., Tsubata, T., Leclercq, L., Stappert, H., and Reth, M.: Molecular components of the B-cell antigen receptor complex of the IgM class. Nature 343: 760–762, 1990

    Google Scholar 

  • Hornbeck, P. and Paul, W. E.: Anti-immunoglobulin and phorbol ester induce phosphorylation of proteins associated with the plasma membrane and cytoskeleton in murine B lymphocytes. J Biol Chem 261: 14817–14824, 1986

    Google Scholar 

  • Huck, S., Fort, P., Crawford, D. H., Lefranc, M.-P., and Lefranc, G.: Sequence of a human immunoglobulin gamma3 heavy chain constant region gene. Comparison with the other human C gamma genes. Nucleic Acids Res 14: 1779–1789, 1986

    Google Scholar 

  • Huck, S., Lefranc, G., and Lefranc, M.-P.: A human immunoglobulin IGHG3 allele (Gmb0, b1, c3, c5, u) with an IGHG4 converted region and three hinge exons. Immunogenetics 30: 250–257, 1989

    Google Scholar 

  • Ishida, N., Ueda, S., Hayashida, H., Miyata, T., and Honjo, T.: The nucleotide sequence of the mouse immunoglobulin epsilon gene: comparison with the human epsilon gene sequence. EMBO J 1: 1117–1123, 1982

    Google Scholar 

  • Jeffreys, A. J., Neumann, R., and Wilson, V.: Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60: 473–485, 1990

    Google Scholar 

  • Kehry, M., Ewald, S., Douglas, R., Sibley, C., Raschke, W., Fambrough, D., and Hood, L.: The immunoglobulin μ chains of membrane-bound and secreted IgM molecules differ in their C-terminal segments. Cell 21: 393–406, 1980

    Google Scholar 

  • Kirsch, I. R., Morton, C. C., Nakahara, K., and Leder, P.: Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science 216: 301–303, 1982

    Google Scholar 

  • Komaromy, M., Clayton, L., Rogers, J., Robertson, S., Kettman, J., and Wall, R.: The structure of the mouse immunoglobulin in gamma3 gene segment. Nucleic Acids Res 11: 6775–6785, 1983

    Google Scholar 

  • Krangel, M. S., Bierer, B. E., Devlin, P., Clabby, M., Strominger, J. L., McLean, J., and Brenner, M. B.: T3 glycoprotein is functional although structurally distinct on human T-cell receptor γ T lympocytes. Proc Natl Acad Sci USA 84: 3817–3821, 1987

    Google Scholar 

  • Lefranc, M.-P. and Rabbitts, T. H.: Human immunoglobulin heavy chain A2 gene allotype determination by restriction fragment length polymorphism. Nucleic Acids Res 12: 1303–1311, 1984

    Google Scholar 

  • Lefranc, M.-P., Lefranc, G., and Rabbitts, T. H.: Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature 300: 760–762, 1982

    Google Scholar 

  • Lefranc, M.-P., Lefranc, G., De Lange, G., Out, T. A., Van den Broek, P. J., Van Nieuwkoop, J., Radl, J., Helal, A. N., Chaabani, H., Van Loghem, E., and Rabbitts, T. H.: Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions. Mol Biol Med 1: 207–217, 1983

    Google Scholar 

  • Marusic-Galesic, S., Pardoll, D. M., Saito, T., Oberdan, L., Fowlkes, B. J., Coligan, J., Germain, R. N., Schwartz, R. H., and Kruisbeek, A. M.: Activation properties of T cell receptor-γδ hybridomas expressing diversity in both γ- and δ-chains. J Immunol 140: 411–418, 1988

    Google Scholar 

  • Max, E. E., Battey, J., Ney, R., Kirsch, I. R., and Leder, P.: Duplication and deletion in the human immunoglobulin epsilon genes. Cell 129: 691–699, 1982

    Google Scholar 

  • Milstein, C. P., Deverson, E. V., and Rabbitts, T. H.: The sequence of the human immunoglobulin μ-δ intron reveals possible vestigial switch segments. Nucleic Acids Res 12: 6523–6535, 1984

    Google Scholar 

  • Mount, S. M.: A catalogue of splice junction sequences. Nucleic Acids Res 10: 459–472, 1982

    CAS  PubMed  Google Scholar 

  • Nel, A. E., Wooten, M. W., Landreth, G. E., Goldschmitt-Clermont, P. J., Stevenson, H. C., Miller, P. J., and Galbraith, R. M.: Translocation of phospholipid/Ca2+ dependent protein kinase in B lymphocytes activated by phorbol ester or cross-linking of membrane immunoglobulin. Biochem J 233: 145–149, 1986

    Google Scholar 

  • Rabbitts, T. H., Forster, A., and Milstein, C. P.: Human immunologlobulin heavy chain genes: evolutionary comparisons of Cmu, Cdelta and Cgamma genes and associated switch sequences. Nucleic Acids Res 9: 4509–4524, 1981

    Google Scholar 

  • Ravetch, J. V., Kirsch, I. R., and Leder, P.: Evolutionary approach to the question of immunoglobulin heavy chain switching: evidence from cloned human and mouse genes. Genetics 77: 6734–6738, 1980

    Google Scholar 

  • Reth, M.: Antigen receptor tail clue. Nature 338: 383–384, 1989

    Google Scholar 

  • Riley, D. E.: Very rapid nucleotide sequence analysis of improved, double stranded miniprep. Gene 75: 193–196, 1989

    Google Scholar 

  • Rogers, J., Early, P., Carter, C., Calame, K., Bond, M., Hood, L., and Wall, R.: Two mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain. Cell 20: 303–312, 1980

    Article  CAS  PubMed  Google Scholar 

  • Rogers, J., Choi, E., Souza, L., Carter, C., Word, C., Kuehl, M., Eisenberg, D., and Wall, R.: Gene segments encoding transmembrane carboxyl termini of immunoglobulin gamma chains. Cell 26: 20–27, 1981

    Google Scholar 

  • Sakaguchi, N., Kashiwamura, S., Kimoto, M., Thalmann, P., and Melchers, F.: B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J 7: 3457–3464, 1988

    Google Scholar 

  • Sanger, F., Coulson, A. R., Barrell, B. G., Smith, A. J. H., and Roe, B. A.: Cloning in single stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol 143: 643–646, 1981

    Google Scholar 

  • Singer, P. W., Singer, H. H., and Williamson, A. R.: Different species of messenger RNA encode receptor and secretory IgM μ chains differing at their carboxy termini. Nature 285: 294–300, 1980

    Google Scholar 

  • Smith, G. P.: Evolution of repeated DNA sequences by unequal crossover. Science 191: 528–535, 1976

    CAS  PubMed  Google Scholar 

  • Steinmetz, M., Frelinger, J. G., Fisher, D., Hunkapiller, T., Pereira, D., Weissman, S. M., Uehara, H., Nathenson, S., and Hood, L.: Three cDNA clones encoding mouse transplantation antigens: homology to immunoglobulin genes. Cell 24: 125–134, 1981

    Google Scholar 

  • Tyler, B. M., Cowman, A. F., Gerondakis, S. D., Adams, J. M., and Bernard, O.: mRNA for surface immunoglobulin gamma chains encodes a highly conserved transmembrane sequence and a 28-residue intracellular domain. Proc Natl Acad Sci USA 79: 2008–2012, 1982

    Google Scholar 

  • Vieira, J. and Messing, J.: The pUC plasmids, an M13 mp7 derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene 19: 259–268, 1982

    Google Scholar 

  • Walters, C. S. and Wigzell, H.: Demonstration of heavy and light chain antigenic determinants on the cell-bound receptor for antigen similarities between membrane-attached and humoral antibodies produced by the same cell. J Exp Med 132: 1233–1249, 1970

    Google Scholar 

  • White, M. B., Shen, A. L., Word, C. J., Tucker, P. W., and Blattner, F. R.: Human immunoglobulin D: genomic sequence of the delta heavy chain. Science 228: 733–737, 1985

    CAS  PubMed  Google Scholar 

  • Wienands, J., Hombach, J., Radbruch, A., Riesterer, C., and Reth, M.: Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM. EMBO J 9: 449–455, 1990

    Google Scholar 

  • Word, C. J., Mushinski, J. F., and Tucker, P. W.: The murine immunoglobulin alpha gene expresses multiple transcripts from a unique membrane exon. EMBO J 2: 887–898, 1983

    Google Scholar 

  • Word, C. J., White, M. B., Kusiel, W. A., Shen, A. L., Blattner, F. R., and Tucker, P. W.: The human immunoglobulin Cmu-Cdelta locus: complete nucleotide sequence and structural analysis. Int Immunol 1: 296–309, 1989

    Google Scholar 

  • Yamawaki-Kataoka, Y., Nakai, S., Miyata, T., and Honjo, T.: Nucleotide sequences of gene segments encoding membrane domains of immunoglobulin gamma chains. Proc Natl Acad Sci USA 79: 2623–2627, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers M35288-91.

Address correspondence and offprint requests to: M.-P. Lefranc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bensmana, M., Lefranc, MP. Gene segments encoding membrane domains of the human immunoglobulin gamma 3 and alpha chains. Immunogenetics 32, 321–330 (1990). https://doi.org/10.1007/BF00211646

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00211646

Keywords

Navigation