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. 1991 Jul 15;88(14):6284–6288. doi: 10.1073/pnas.88.14.6284

Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

N Nishimoto 1, H Kubagawa 1, T Ohno 1, G L Gartland 1, A K Stankovic 1, M D Cooper 1
PMCID: PMC52067  PMID: 1906177

Abstract

Precursors of B cells, which constitute a subpopulation of the lymphocytes in bone marrow, can be identified by their surface expression of nonimmunoglobulin markers and the absence of immunoglobulin kappa and lambda light chains. Most pre-B cells synthesize mu heavy chains but, without light-chain partners, these undergo rapid cytoplasmic degradation. In the present study, we demonstrate that late stage pre-B cells, like their neoplastic counterparts, express low levels of a surface receptor composed of mu chains paired with a surrogate light-chain complex formed by Vpre-B and lambda 5-like proteins. The data define a previously suspected but unrecognized stage in normal pre-B-cell differentiation. Expression of a clonally diverse receptor renders this population of immature B-lineage cells potentially vulnerable to clonal selection by antigens and idiotypic interactions.

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Selected References

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

  1. Alt F. W., Blackwell T. K., Yancopoulos G. D. Development of the primary antibody repertoire. Science. 1987 Nov 20;238(4830):1079–1087. doi: 10.1126/science.3317825. [DOI] [PubMed] [Google Scholar]
  2. Bauer S. R., D'Hoostelaere L. A., Melchers F. Conservation of the organization of the pre-B cell specific VpreB1/VpreB2/lambda 5 loci in the genus Mus. Curr Top Microbiol Immunol. 1988;137:130–135. doi: 10.1007/978-3-642-50059-6_19. [DOI] [PubMed] [Google Scholar]
  3. Bauer S. R., Kudo A., Melchers F. Structure and pre-B lymphocyte restricted expression of the VpreB in humans and conservation of its structure in other mammalian species. EMBO J. 1988 Jan;7(1):111–116. doi: 10.1002/j.1460-2075.1988.tb02789.x. [DOI] [PMC free article] [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. Cherayil B. J., Pillai S. The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. J Exp Med. 1991 Jan 1;173(1):111–116. doi: 10.1084/jem.173.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Cooper M. D. Pre-B cells; normal and abnormal development. J Clin Immunol. 1981 Apr;1(2):81–89. doi: 10.1007/BF00915383. [DOI] [PubMed] [Google Scholar]
  8. Duperray C., Boiron J. M., Boucheix C., Cantaloube J. F., Lavabre-Bertrand T., Attal M., Brochier J., Maraninchi D., Bataille R., Klein B. The CD24 antigen discriminates between pre-B and B cells in human bone marrow. J Immunol. 1990 Dec 1;145(11):3678–3683. [PubMed] [Google Scholar]
  9. Forni L., Cazenave P. A., Cosenza H., Forsbeck K., Coutinho A. Expression of V-region-like determinants on Ig-negative precursors in murine fetal liver and bone marrow. Nature. 1979 Jul 19;280(5719):241–243. doi: 10.1038/280241a0. [DOI] [PubMed] [Google Scholar]
  10. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  11. Hollis G. F., Evans R. J., Stafford-Hollis J. M., Korsmeyer S. J., McKearn J. P. Immunoglobulin lambda light-chain-related genes 14.1 and 16.1 are expressed in pre-B cells and may encode the human immunoglobulin omega light-chain protein. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5552–5556. doi: 10.1073/pnas.86.14.5552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Karasuyama H., Kudo A., Melchers F. The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain. J Exp Med. 1990 Sep 1;172(3):969–972. doi: 10.1084/jem.172.3.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kearney J. F., Vakil M. Idiotype-directed interactions during ontogeny play a major role in the establishment of the adult B cell repertoire. Immunol Rev. 1986 Dec;94:39–50. doi: 10.1111/j.1600-065x.1986.tb01163.x. [DOI] [PubMed] [Google Scholar]
  15. Kerr W. G., Cooper M. D., Feng L., Burrows P. D., Hendershot L. M. Mu heavy chains can associate with a pseudo-light chain complex (psi L) in human pre-B cell lines. Int Immunol. 1989;1(4):355–361. doi: 10.1093/intimm/1.4.355. [DOI] [PubMed] [Google Scholar]
  16. Kubagawa H., Gathings W. E., Levitt D., Kearney J. F., Cooper M. D. Immunoglobulin isotype expression of normal pre-B cells as determined by immunofluorescence. J Clin Immunol. 1982 Oct;2(4):264–269. doi: 10.1007/BF00915065. [DOI] [PubMed] [Google Scholar]
  17. Kudo A., Melchers F. A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J. 1987 Aug;6(8):2267–2272. doi: 10.1002/j.1460-2075.1987.tb02500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Loken M. R., Shah V. O., Dattilio K. L., Civin C. I. Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development. Blood. 1987 Nov;70(5):1316–1324. [PubMed] [Google Scholar]
  19. Mami F., Cazenave P. A., Kindt T. J. Conservation of the immunoglobulin C lambda 5 gene in the Mus gene. EMBO J. 1988 Jan;7(1):117–122. doi: 10.1002/j.1460-2075.1988.tb02790.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matsuo T., Kimoto M., Sakaguchi N. Direct identification of the putative surface IgM receptor-associated molecule encoded by murine B cell-specific mb-1 gene. J Immunol. 1991 Mar 1;146(5):1584–1590. [PubMed] [Google Scholar]
  21. Melchers F., Von Boehmer H., Phillips R. A. B-lymphocyte subpopulations in the mouse. Organ distribution and ontogeny of immunoglobulin-synthesizing and of mitogen-sensitive cells. Transplant Rev. 1975;25:26–58. doi: 10.1111/j.1600-065x.1975.tb00725.x. [DOI] [PubMed] [Google Scholar]
  22. Misener V., Jongstra-Bilen J., Young A. J., Atkinson M. J., Wu G. E., Jongstra J. Association of Ig L chain-like protein lambda 5 with a 16-kilodalton protein in mouse pre-B cell lines is not dependent on the presence of Ig H chain protein. J Immunol. 1990 Aug 1;145(3):905–909. [PubMed] [Google Scholar]
  23. Ohno T., Cooper M. D., Kubagawa H. A mouse monoclonal antibody reactive preferentially with human IgM lambda. Hybridoma. 1990 Oct;9(5):473–480. doi: 10.1089/hyb.1990.9.473. [DOI] [PubMed] [Google Scholar]
  24. Paige C. J., Kincade P. W., Ralph P. Independent control of immunoglobulin heavy and light chain expression in a murine pre-B-cell line. Nature. 1981 Aug 13;292(5824):631–633. doi: 10.1038/292631a0. [DOI] [PubMed] [Google Scholar]
  25. Pillai S., Baltimore D. Formation of disulphide-linked mu 2 omega 2 tetramers in pre-B cells by the 18K omega-immunoglobulin light chain. Nature. 1987 Sep 10;329(6135):172–174. doi: 10.1038/329172a0. [DOI] [PubMed] [Google Scholar]
  26. Raff M. C., Megson M., Owen J. J., Cooper M. D. Early production of intracellular IgM by B-lymphocyte precursors in mouse. Nature. 1976 Jan 22;259(5540):224–226. doi: 10.1038/259224a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Rosenberg Y. J., Parish C. R. Ontogeny of the antibody-forming cell line in mice. IV. Appearance of cells bearing Fc receptors, complement receptors, and surface immunoglobulin. J Immunol. 1977 Feb;118(2):612–617. [PubMed] [Google Scholar]
  29. Sakaguchi N., Berger C. N., Melchers F. Isolation of a cDNA copy of an RNA species expressed in murine pre-B cells. EMBO J. 1986 Sep;5(9):2139–2147. doi: 10.1002/j.1460-2075.1986.tb04477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schiff C., Milili M., Fougereau M. Isolation of early immunoglobulin lambda-like gene transcripts in human fetal liver. Eur J Immunol. 1989 Oct;19(10):1873–1878. doi: 10.1002/eji.1830191018. [DOI] [PubMed] [Google Scholar]
  31. Takemori T., Mizuguchi J., Miyazoe I., Nakanishi M., Shigemoto K., Kimoto H., Shirasawa T., Maruyama N., Taniguchi M. Two types of mu chain complexes are expressed during differentiation from pre-B to mature B cells. EMBO J. 1990 Aug;9(8):2493–2500. doi: 10.1002/j.1460-2075.1990.tb07428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Thorens B., Schulz M. F., Vassalli P. Bone marrow pre-B lymphocytes synthesize immunoglobulin mu chains of membrane type with different properties and intracellular pathways. EMBO J. 1985 Feb;4(2):361–368. doi: 10.1002/j.1460-2075.1985.tb03637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tsubata T., Reth M. The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface. J Exp Med. 1990 Sep 1;172(3):973–976. doi: 10.1084/jem.172.3.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Villablanca J. G., Anderson J. M., Moseley M., Law C. L., Elstrom R. L., LeBien T. W. Differentiation of normal human pre-B cells in vitro. J Exp Med. 1990 Jul 1;172(1):325–334. doi: 10.1084/jem.172.1.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vogler L. B., Crist W. M., Bockman D. E., Pearl E. R., Lawton A. R., Cooper M. D. Pre-B-cell leukemia. A new phenotype of childhood lymphoblastic leukemia. N Engl J Med. 1978 Apr 20;298(16):872–878. doi: 10.1056/NEJM197804202981603. [DOI] [PubMed] [Google Scholar]
  36. Ward E. S., Güssow D., Griffiths A. D., Jones P. T., Winter G. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature. 1989 Oct 12;341(6242):544–546. doi: 10.1038/341544a0. [DOI] [PubMed] [Google Scholar]
  37. Wienands J., Hombach J., Radbruch A., Riesterer C., Reth M. Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM. EMBO J. 1990 Feb;9(2):449–455. doi: 10.1002/j.1460-2075.1990.tb08130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yellen A. J., Glenn W., Sukhatme V. P., Cao X. M., Monroe J. G. Signaling through surface IgM in tolerance-susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice. J Immunol. 1991 Mar 1;146(5):1446–1454. [PubMed] [Google Scholar]

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