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. 1985 Nov 1;162(5):1620–1633. doi: 10.1084/jem.162.5.1620

Strain-specific silencing of a predominant antidextran clonotype family

PMCID: PMC2187924  PMID: 2414388

Abstract

The immune response to dextran is characterized by marked phenotypic differences among murine strains. In particular, Igha strains, as opposed to strains of other Igh haplotypes, respond relatively vigorously to dextran B1355 fraction S (DEX), producing predominantly antibodies bearing the lambda light chain, and specific for the alpha(1- ---3) glucose linkage. We have investigated this disparity in BALB/c (Igha) vs. C.B20 (Ighb) mice at the individual precursor cell level. Consistent with previous findings (7-9, 35, 40, 42, 43), there was a 10- fold higher frequency of lambda-bearing splenic B cells specific for the alpha(1----3) linkage in Igha mice. As with previously studied (25- 27) predominant specificities, the origin of this high frequency of lambda-bearing alpha(1----3) DEX-specific B cells appears to be a reflection of a high expression of this specificity in surface Ig (sIg)- negative cells emerging from the bone marrow generative cell pool. Surprisingly, although C.B20 mice (Ighb) have a low frequency of lambda- bearing alpha(1----3) DEX-specific B cells in their mature primary splenic population, the frequency of precursor cells of this clonotype in their sIg- bone marrow cell population is equivalent to that of BALB/c sIg- cells. These cells could only be stimulated in allotype allogeneic (Igha), as opposed to allotype syngeneic (Ighb), carrier- primed irradiated recipients. This finding was confirmed by the finding that a high proportion of antidextran hybridoma cell lines derived from C.B20 bone marrow cells produced lambda-bearing alpha(1----3) DEX- specific antibodies that were IdX+. These findings have led us to conclude that the well-established phenotypic difference between Igha and Ighb mice with respect to the expression of lambda-bearing alpha(1-- --3) DEX-specific antibody responses is not, as previously assumed, the result of an inability of Ighb mice to generate B cells of this clonotype, but rather, is the product of environmental, possibly antiidiotypic, silencing of cells of this clonotype as they mature in Ighb mice.

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Selected References

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  1. Accolla R. S., Gearhart P. J., Sigal N. H., Cancro M. P., Klinman N. R. Idiotype-specific neonatal suppression of phosphorylcholine-responsive B cells. Eur J Immunol. 1977 Dec;7(12):876–881. doi: 10.1002/eji.1830071211. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blomberg B., Geckeler W. R., Weigert M. Genetics of the antibody response to dextran in mice. Science. 1972 Jul 14;177(4044):178–180. doi: 10.1126/science.177.4044.178. [DOI] [PubMed] [Google Scholar]
  4. Bluestone J. A., Auchincloss H., Jr, Cazenave P. A., Ozato K., Sachs D. H. Anti-idiotypes to monoclonal anti-H-2 antibodies. III. Syngeneic anti-idiotypes on antibodies induced by in vivo administration of xenogeneic anti-idiotypes. J Immunol. 1982 Nov;129(5):2066–2068. [PubMed] [Google Scholar]
  5. Bona C. A., Heber-Katz E., Paul W. E. Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones. J Exp Med. 1981 Apr 1;153(4):951–967. doi: 10.1084/jem.153.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brack C., Hirama M., Lenhard-Schuller R., Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978 Sep;15(1):1–14. doi: 10.1016/0092-8674(78)90078-8. [DOI] [PubMed] [Google Scholar]
  7. Cambier J. C., Kettman J. R., Vitetta E. S., Uhr J. W. Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance. J Exp Med. 1976 Jul 1;144(1):293–297. doi: 10.1084/jem.144.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cancro M. P., Gerhard W., Klinman N. R. The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. J Exp Med. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cancro M. P., Sigal N. H., Klinman N. R. Differential expression of an equivalent clonotype among BALB/c and C57BL/6 mice. J Exp Med. 1978 Jan 1;147(1):1–12. doi: 10.1084/jem.147.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coleclough C., Cooper D., Perry R. P. Rearrangement of immunoglobulin heavy chain genes during B-lymphocyte development as revealed by studies of mouse plasmacytoma cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1422–1426. doi: 10.1073/pnas.77.3.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cosenza H., Köhler H. Specific suppression of the antibody response by antibodies to receptors. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2701–2705. doi: 10.1073/pnas.69.9.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. D'Hoostelaere L., Potter M. Genetics of the alpha 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice. J Immunol. 1982 Jan;128(1):492–497. [PubMed] [Google Scholar]
  13. Denis K. A., Klinman N. R. Genetic and temporal control of neonatal antibody expression. J Exp Med. 1983 Apr 1;157(4):1170–1183. doi: 10.1084/jem.157.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  15. Eichmann K. Expression and function of idiotypes of lymphocytes. Adv Immunol. 1978;26:195–254. doi: 10.1016/s0065-2776(08)60231-x. [DOI] [PubMed] [Google Scholar]
  16. Epstein R., Lehmann K., Cohn M. Induction of lambda 1-immunoglobulin is determined by a regulatory gene (r lambda 1) linked (or identical) to the structural (c lambda 1) gene. J Exp Med. 1983 May 1;157(5):1681–1686. doi: 10.1084/jem.157.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  18. Gearhart P. J., Sigal N. H., Klinman N. R. Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level. J Exp Med. 1975 Jan 1;141(1):56–71. doi: 10.1084/jem.141.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hiernaux J., Bona C., Baker P. J. Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone. J Exp Med. 1981 Apr 1;153(4):1004–1008. doi: 10.1084/jem.153.4.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Juy D., Primi D., Sanchez P., Cazenave P. A. The selection and maintenance of the V region determinant repertoire is germ-line encoded and T cell-independent. Eur J Immunol. 1983 Apr;13(4):326–331. doi: 10.1002/eji.1830130410. [DOI] [PubMed] [Google Scholar]
  21. Kelsoe G., Reth M., Rajewsky K. Control idiotope expression by monoclonal anti-idiotope antibodies. Immunol Rev. 1980;52:75–88. doi: 10.1111/j.1600-065x.1980.tb00331.x. [DOI] [PubMed] [Google Scholar]
  22. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  23. Klinman N. R., Riley R. L., Stone M. R., Wylie D., Zharhary D. The specificity repertoire of prereceptor and mature B cells. Ann N Y Acad Sci. 1983;418:130–139. doi: 10.1111/j.1749-6632.1983.tb18061.x. [DOI] [PubMed] [Google Scholar]
  24. Klinman N. R., Schrater A. F., Katz D. H. Immature B cells as the target for in vivo tolerance induction. J Immunol. 1981 May;126(5):1970–1973. [PubMed] [Google Scholar]
  25. Klinman N. R., Stone M. R. Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire. J Exp Med. 1983 Dec 1;158(6):1948–1961. doi: 10.1084/jem.158.6.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Köhler H. The response to phosphorylcholine: dissecting an immune response. Transplant Rev. 1975;27:24–56. [PubMed] [Google Scholar]
  27. Laskin J. A., Gray A., Nisonoff A., Klinman N. R., Gottlieb P. D. Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4600–4604. doi: 10.1073/pnas.74.10.4600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Leo O., Slaoui M., Marvel J., Milner E. C., Hiernaux J., Moser M., Capra J. D., Urbain J. Idiotypic analysis of polyclonal and monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain. J Immunol. 1985 Mar;134(3):1734–1739. [PubMed] [Google Scholar]
  29. Lieberman R., Potter M., Mushinski E. B., Humphrey W., Jr, Rudikoff S. Genetics of a new IgVH (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholine. J Exp Med. 1974 Apr 1;139(4):983–1001. doi: 10.1084/jem.139.4.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
  31. McGuire K. L., Vitetta E. S. kappa/lambda Shifts do not occur during maturation of murine B cells. J Immunol. 1981 Oct;127(4):1670–1673. [PubMed] [Google Scholar]
  32. Meek K., Jeske D., Slaoui M., Leo O., Urbain J., Capra J. D. Complete amino acid sequence of heavy chain variable regions derived from two monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain. J Exp Med. 1984 Oct 1;160(4):1070–1086. doi: 10.1084/jem.160.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Metcalf E. S., Klinman N. R. In vitro tolerance induction of bone marrow cells: a marker for B cell maturation. J Immunol. 1977 Jun;118(6):2111–2116. [PubMed] [Google Scholar]
  34. Metcalf E. S., Klinman N. R. In vitro tolerance induction of neonatal murine B cells. J Exp Med. 1976 Jun 1;143(6):1327–1340. doi: 10.1084/jem.143.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mäkelä O., Karjalainen K. Inherited immunoglobulin idiotypes of the mouse. Immunol Rev. 1977;34:119–138. doi: 10.1111/j.1600-065x.1977.tb00370.x. [DOI] [PubMed] [Google Scholar]
  36. Near R. I., Manser T., Gefter M. L. The generation of major and minor idiotype-bearing families of anti-p-azophenylarsonate antibodies; stochastic utilization of VH gene segments. J Immunol. 1985 Mar;134(3):2004–2009. [PubMed] [Google Scholar]
  37. Nishikawa S., Takemori T., Rajewsky K. The expression of a set of antibody variable regions in lipopolysaccharide-reactive B cells at various stages of ontogeny and its control by anti-idiotypic antibody. Eur J Immunol. 1983 Apr;13(4):318–325. doi: 10.1002/eji.1830130409. [DOI] [PubMed] [Google Scholar]
  38. Nossal G. J., Pike B. L. Evidence for the clonal abortion theory of B-lymphocyte tolerance. J Exp Med. 1975 Apr 1;141(4):904–917. [PMC free article] [PubMed] [Google Scholar]
  39. Pawlak L. L., Nisonoff A. Distribution of a cross-reactive idiotypic specificity in inbred strains of mice. J Exp Med. 1973 Apr 1;137(4):855–869. doi: 10.1084/jem.137.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pène J., Bekkhoucha F., Desaymard C., Zaghouani H., Stanislawski M. Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross-reactive idiotype antibodies. J Exp Med. 1983 May 1;157(5):1573–1593. doi: 10.1084/jem.157.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Raychaudhuri S., Cancro M. P. Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12. J Exp Med. 1985 Apr 1;161(4):816–831. doi: 10.1084/jem.161.4.816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Riblet R., Blomberg B., Weigert M., Lieberman R., Taylor B. A., Potter M. Genetics of mouse antibodies. I. Linkage of the dextran response locus, VH-DEX, to allotype. Eur J Immunol. 1975 Nov;5(11):775–777. doi: 10.1002/eji.1830051109. [DOI] [PubMed] [Google Scholar]
  43. Riblet R., Weigert M., Mäkelä O. Genetics of mouse antibodies. II. Recombination between VH genes and allotype. Eur J Immunol. 1975 Nov;5(11):778–781. doi: 10.1002/eji.1830051110. [DOI] [PubMed] [Google Scholar]
  44. Riley R. L., Wylie D. E., Klinman N. R. B cell repertoire diversification precedes immunoglobulin receptor expression. J Exp Med. 1983 Nov 1;158(5):1733–1738. doi: 10.1084/jem.158.5.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rubinstein L. J., Yeh M., Bona C. A. Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells. J Exp Med. 1982 Aug 1;156(2):506–521. doi: 10.1084/jem.156.2.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Seidman J. G., Leder A., Nau M., Norman B., Leder P. Antibody diversity. Science. 1978 Oct 6;202(4363):11–17. doi: 10.1126/science.99815. [DOI] [PubMed] [Google Scholar]
  47. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  48. Sigal N. H., Klinman N. R. The B-cell clonotype repertoire. Adv Immunol. 1978;26:255–337. doi: 10.1016/s0065-2776(08)60232-1. [DOI] [PubMed] [Google Scholar]
  49. Sigal N. H. Regulation of azophenylarsonate-specific repertoire expression. 1. Frequency of cross-reactive idiotype-positive B cells in A/J and BALB/c mice. J Exp Med. 1982 Nov 1;156(5):1352–1365. doi: 10.1084/jem.156.5.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Stohrer R., Kearney J. F. Fine idiotype analysis of B cell precursors in the T-dependent and T-independent responses to alpha 1-3 dextran in BALB/c mice. J Exp Med. 1983 Dec 1;158(6):2081–2094. doi: 10.1084/jem.158.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Walker S. M., Meinke G. C., Weigle W. O. Separation of various B-cell subpopulations from mouse spleen. I. Depletion of B cells by rosetting with glutaraldehyde-fixed, anti-immunoglobulin-coupled red blood cells. Cell Immunol. 1979 Aug;46(1):158–169. doi: 10.1016/0008-8749(79)90253-3. [DOI] [PubMed] [Google Scholar]
  52. Ward R. E., Kearney J. F., Köhler H. Light chain isotypes selectively associate with heavy chain idiotypes in T-dependent and T-independent dextran-specific precursors. Nature. 1981 Aug 13;292(5824):629–631. doi: 10.1038/292629a0. [DOI] [PubMed] [Google Scholar]
  53. Ward R., Kohler H. Regulation of clones responding to dextran B1355S. II. Response of T-dependent and T-independent precursors. J Immunol. 1981 Jan;126(1):146–149. [PubMed] [Google Scholar]
  54. Wysocki L. J., Margolies M. N., Huang B., Nemazee D. A., Wechsler D. S., Sato V. L., Smith J. A., Gefter M. L. Combinational diversity within variable regions bearing the predominant anti-p-azophenylarsonate idiotype of strain A mice. J Immunol. 1985 Apr;134(4):2740–2747. [PubMed] [Google Scholar]
  55. Zharhary D., Klinman N. R. Antigen responsiveness of the mature and generative B cell populations of aged mice. J Exp Med. 1983 Apr 1;157(4):1300–1308. doi: 10.1084/jem.157.4.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]

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