Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1990 Feb;9(2):449–455. doi: 10.1002/j.1460-2075.1990.tb08130.x

Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM.

J Wienands 1, J Hombach 1, A Radbruch 1, C Riesterer 1, M Reth 1
PMCID: PMC551686  PMID: 2303036

Abstract

Two classes of immunoglobulin, IgM and IgD, are present as antigen receptors on the surface of mature B lymphocytes. We show here that IgD molecules are noncovalently associated in the B cell membrane with a heterodimer consisting of two proteins of 35 kd (IgD-alpha) and 39 kd (Ig-beta), respectively. The two novel proteins are not found in the IgD-expressing myeloma J558L delta m, which fails to bring IgD antigen receptor onto the cell surface. In a surface IgD positive variant line of this myeloma, however, membrane-bound IgD molecules are associated with the heterodimer, suggesting that the formation of an antigen receptor complex is required for surface IgD expression. We further demonstrate that the IgD-associated heterodimer differs partly from that of the IgM antigen receptor and that its binding to the heavy chain only requires the presence of the last constant domain and the transmembrane part of the delta m chain.

Full text

PDF
451

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alés-Martínez J. E., Warner G. L., Scott D. W. Immunoglobulins D and M mediate signals that are qualitatively different in B cells with an immature phenotype. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6919–6923. doi: 10.1073/pnas.85.18.6919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ayane M., Nielsen P., Köhler G. Cloning and sequencing of mouse ribosomal protein S12 cDNA. Nucleic Acids Res. 1989 Aug 25;17(16):6722–6722. doi: 10.1093/nar/17.16.6722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cambier J. C., Monroe J. G. B cell activation. V. Differentiation signaling of B cell membrane depolarization, increased I-A expression, G0 to G1 transition, and thymidine uptake by anti-IgM and anti-IgD antibodies. J Immunol. 1984 Aug;133(2):576–581. [PubMed] [Google Scholar]
  4. Campbell K. S., Cambier J. C. B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex. EMBO J. 1990 Feb;9(2):441–448. doi: 10.1002/j.1460-2075.1990.tb08129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheng H. L., Blattner F. R., Fitzmaurice L., Mushinski J. F., Tucker P. W. Structure of genes for membrane and secreted murine IgD heavy chains. Nature. 1982 Apr 1;296(5856):410–415. doi: 10.1038/296410a0. [DOI] [PubMed] [Google Scholar]
  6. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  7. Coffman R. L., Cohn M. The class of surface immunoglobulin on virgin and memory B lymphocytes. J Immunol. 1977 May;118(5):1806–1815. [PubMed] [Google Scholar]
  8. Cooper M. D., Kearney J. F., Gathings W. E., Lawton A. R. Effects of anti-Ig antibodies on the development and differentiation of B cells. Immunol Rev. 1980;52:29–53. doi: 10.1111/j.1600-065x.1980.tb00329.x. [DOI] [PubMed] [Google Scholar]
  9. Goding J. W., Layton J. E. Antigen-induced co-capping of IgM and IgD-like receptors on murine B cells. J Exp Med. 1976 Sep 1;144(3):852–857. doi: 10.1084/jem.144.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goodnow C. C., Crosbie J., Adelstein S., Lavoie T. B., Smith-Gill S. J., Brink R. A., Pritchard-Briscoe H., Wotherspoon J. S., Loblay R. H., Raphael K. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988 Aug 25;334(6184):676–682. doi: 10.1038/334676a0. [DOI] [PubMed] [Google Scholar]
  11. Hombach J., Leclercq L., Radbruch A., Rajewsky K., Reth M. A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells. EMBO J. 1988 Nov;7(11):3451–3456. doi: 10.1002/j.1460-2075.1988.tb03219.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hombach J., Sablitzky F., Rajewsky K., Reth M. Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface. J Exp Med. 1988 Feb 1;167(2):652–657. doi: 10.1084/jem.167.2.652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kearney J. F., Cooper M. D., Klein J., Abney E. R., Parkhouse R. M., Lawton A. R. Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice. J Exp Med. 1977 Jul 1;146(1):297–301. doi: 10.1084/jem.146.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krangel M. S., Bierer B. E., Devlin P., Clabby M., Strominger J. L., McLean J., Brenner M. B. T3 glycoprotein is functional although structurally distinct on human T-cell receptor gamma T lymphocytes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3817–3821. doi: 10.1073/pnas.84.11.3817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liu C. P., Tucker P. W., Mushinski J. F., Blattner F. R. Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980 Sep 19;209(4463):1348–1353. doi: 10.1126/science.6774414. [DOI] [PubMed] [Google Scholar]
  16. Lundblad A., Steller R., Kabat E. A., Hirst J. W., Weigert M. G., Cohn M. Immunochemical studies on mouse myeloma proteins with specificity for dextran or for levan. Immunochemistry. 1972 May;9(5):535–544. doi: 10.1016/0019-2791(72)90063-8. [DOI] [PubMed] [Google Scholar]
  17. Marusić-Galesić S., Pardoll D. M., Saito T., Leo O., Fowlkes B. J., Coligan J., Germain R. N., Schwartz R. H., Kruisbeek A. M. Activation properties of T cell receptor-gamma delta hybridomas expressing diversity in both gamma- and delta-chains. J Immunol. 1988 Jan 15;140(2):411–418. [PubMed] [Google Scholar]
  18. Monroe J. G., Cambier J. C. B cell activation. I. Anti-immunoglobulin-induced receptor cross-linking results in a decrease in the plasma membrane potential of murine B lymphocytes. J Exp Med. 1983 Jun 1;157(6):2073–2086. doi: 10.1084/jem.157.6.2073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Monroe J. G., Cambier J. C. B cell activation. II. Receptor cross-linking by thymus-independent and thymus-dependent antigens induces a rapid decrease in the plasma membrane potential of antigen-binding B lymphocytes. J Immunol. 1983 Dec;131(6):2641–2644. [PubMed] [Google Scholar]
  20. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neuberger M. S. Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. EMBO J. 1983;2(8):1373–1378. doi: 10.1002/j.1460-2075.1983.tb01594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nossal G. J. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. doi: 10.1146/annurev.iy.01.040183.000341. [DOI] [PubMed] [Google Scholar]
  23. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perucho M., Hanahan D., Wigler M. Genetic and physical linkage of exogenous sequences in transformed cells. Cell. 1980 Nov;22(1 Pt 1):309–317. doi: 10.1016/0092-8674(80)90178-6. [DOI] [PubMed] [Google Scholar]
  25. Picard D., Schaffner W. Correct transcription of a cloned mouse immunoglobulin gene in vivo. Proc Natl Acad Sci U S A. 1983 Jan;80(2):417–421. doi: 10.1073/pnas.80.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pike B. L., Boyd A. W., Nossal G. J. Clonal anergy: the universally anergic B lymphocyte. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2013–2017. doi: 10.1073/pnas.79.6.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. doi: 10.1038/338383b0. [DOI] [PubMed] [Google Scholar]
  29. Reth M., Hämmerling G. J., Rajewsky K. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur J Immunol. 1978 Jun;8(6):393–400. doi: 10.1002/eji.1830080605. [DOI] [PubMed] [Google Scholar]
  30. Reth M., Petrac E., Wiese P., Lobel L., Alt F. W. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains. EMBO J. 1987 Nov;6(11):3299–3305. doi: 10.1002/j.1460-2075.1987.tb02649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Samelson L. E., Harford J. B., Klausner R. D. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985 Nov;43(1):223–231. doi: 10.1016/0092-8674(85)90027-3. [DOI] [PubMed] [Google Scholar]
  33. Sitia R., Neuberger M. S., Milstein C. Regulation of membrane IgM expression in secretory B cells: translational and post-translational events. EMBO J. 1987 Dec 20;6(13):3969–3977. doi: 10.1002/j.1460-2075.1987.tb02739.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stern C., McConnell I. Immunoglobulins M and D as antigen-binding receptors on the same cell, with shared specificity. Eur J Immunol. 1976 Mar;6(3):225–227. doi: 10.1002/eji.1830060316. [DOI] [PubMed] [Google Scholar]
  35. Tisch R., Roifman C. M., Hozumi N. Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914–6918. doi: 10.1073/pnas.85.18.6914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vasilov R. G., Ploegh H. L. Biosynthesis of murine immunoglobulin D: heterogeneity of glycosylation. Eur J Immunol. 1982 Oct;12(10):804–813. doi: 10.1002/eji.1830121003. [DOI] [PubMed] [Google Scholar]
  37. Vitetta E. S., Uhr J. W. Cell surface immunoglobulin. XV. The presence of IgM and an IgD-like molecule on the same cell in murine lymphoid tissue. Eur J Immunol. 1976 Feb;6(2):140–143. doi: 10.1002/eji.1830060215. [DOI] [PubMed] [Google Scholar]
  38. Vitetta E., Puré E., Isakson P., Buck L., Uhr J. The activation of murine B cells: the role of surface immunoglobulins. Immunol Rev. 1980;52:211–231. doi: 10.1111/j.1600-065x.1980.tb00336.x. [DOI] [PubMed] [Google Scholar]
  39. Yuan D. Regulation of IgM and IgD synthesis in B lymphocytes. II. Translational and post-translational events. J Immunol. 1984 Mar;132(3):1566–1570. [PubMed] [Google Scholar]
  40. Yuan D., Tucker P. W. Regulation of IgM and IgD synthesis in B lymphocytes. I. Changes in biosynthesis of mRNA for mu- and delta-chains. J Immunol. 1984 Mar;132(3):1561–1565. [PubMed] [Google Scholar]
  41. Yuan D., Vitetta E. S. Cell surface immunoglobulin XXI. appearance of IgD on murine lymphocytes during differentiation. J Immunol. 1978 Feb;120(2):353–356. [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES