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. 1982 Nov 1;156(5):1352–1365. doi: 10.1084/jem.156.5.1352

Regulation of azophenylarsonate-specific repertoire expression. 1. Frequency of cross-reactive idiotype-positive B cells in A/J and BALB/c mice

PMCID: PMC2186841  PMID: 6982304

Abstract

A large proportion of p-azophenylarsonate (ARS)-specific antibodies from A/J mice share a cross-reactive idiotype (CRIA) that comprises a family of closely related but nonidentical clonotypes. I determined that only 2.6 % (7 out of 267) A/J ARS-specific monoclonal antibodies generated in the splenic focus system possess the predominant CRIA. Because ARS-specific B cells are present at a frequency of 1/68,000 B cells, the frequency of the entire idiotype family is 1 per 2.8 X 10(6) splenic B cells. Thus, there is a striking discrepancy between the representation of this idiotype at the clonal precursor cell level and the serum antibody response. In addition, BALB/c mice have the potential to generate CRIA-positive precursor cells within their nonimmune repertoire. When A/J mice are immunized with ARS-protein conjugates, the serum antibody response and precursor cell population are both dominated by CRIA. The frequency of CRIA-positive B cells increases over 100-fold after immunization, whereas CRIA-negative precursor cells may initially decrease, followed by a later rise in frequency. Finally, although ARS-specific precursor cells are present in high frequency at birth, CRIA-positive monoclonal anti-ARS antibodies are not observed during the early neonatal period. These data provide evidence to suggest that complex regulatory networks influence precursor cell and serum antibody expression.

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Selected References

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  1. Andres C. M., Maddalena A., Hudak S., Young N. M., Claflin J. L. Anti-phosphocholine hybridoma antibodies. II. Functional analysis of binding sites within three antibody families. J Exp Med. 1981 Nov 1;154(5):1584–1598. doi: 10.1084/jem.154.5.1584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ben-Neriah Y., Cohen J. B., Rechavi G., Zakut R., Givol D. Polymorphism of germ-line immunoglobulin VH genes correlates with allotype and idiotype markers. Eur J Immunol. 1981 Dec;11(12):1017–1020. doi: 10.1002/eji.1830111213. [DOI] [PubMed] [Google Scholar]
  3. Bottomly K., Mosier D. E. Mice whose B cells cannot produce the T15 idiotype also lack an antigen-specific helper T cell required for T15 expression. J Exp Med. 1979 Dec 1;150(6):1399–1409. doi: 10.1084/jem.150.6.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown A. R., Lamoyi E., Nisonoff A. Relationship of idiotypes of the anti-p-azophenylarsonate antibodies of A/J and BALB/c mice. J Immunol. 1981 Apr;126(4):1268–1273. [PubMed] [Google Scholar]
  5. Cancro M. P., Klinman N. R. B cell repertoire ontogeny: heritable but dissimilar development of parental and F1 repertoires. J Immunol. 1981 Mar;126(3):1160–1164. [PubMed] [Google Scholar]
  6. 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]
  7. Cerny J., Wallich R., Hammerling G. J. Analysis of T15 idiotopes by monoclonal antibodies: variability of idiotopic expression on phosphorylcholine-specific lymphocytes from individual inbred mice. J Immunol. 1982 Apr;128(4):1885–1891. [PubMed] [Google Scholar]
  8. Claflin J. L. Uniformity in the clonal repertoire for the immune response to phosphorylcholine in mice. Eur J Immunol. 1976 Oct;6(10):669–674. doi: 10.1002/eji.1830061002. [DOI] [PubMed] [Google Scholar]
  9. Conger J. D., Lewis G. K., Goodman J. W. Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque-forming cells. J Exp Med. 1981 May 1;153(5):1173–1186. doi: 10.1084/jem.153.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
  11. Estess P., Lamoyi E., Nisonoff A., Capra J. D. Structural studies on induced antibodies with defined idiotypic specificities. IX. Framework differences in the heavy- and light-chain-variable regions of monoclonal anti-p-azophenylarsonate antibodies from A/J mice differing with respect to a cross-reactive idiotype. J Exp Med. 1980 Apr 1;151(4):863–875. doi: 10.1084/jem.151.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gill-Pazaris L. A., Lamoyi E., Brown A. R., Nisonoff A. Properties of a minor cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice. J Immunol. 1981 Jan;126(1):75–79. [PubMed] [Google Scholar]
  13. Hart D. A., Pawlak L. L., Nisonoff A. Nature of anti-hapten antibodies arising after immune suppression of a set of cross-raactive idiotypic specificities. Eur J Immunol. 1973 Jan;3(1):44–48. doi: 10.1002/eji.1830030110. [DOI] [PubMed] [Google Scholar]
  14. Ju S. T., Pierres M., Germain R. N., Benacerraf B., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. VII. Common idiotype on hybridoma antibodies to poly(Glu60 Ala40) J Immunol. 1980 Sep;125(3):1230–1236. [PubMed] [Google Scholar]
  15. Ju S., Gray A., Nisonoff A. Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype. J Exp Med. 1977 Mar 1;145(3):540–556. doi: 10.1084/jem.145.3.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kapsalis A. A., Tung A. S., Nisonoff A. Relative combining affinities of anti-p-azophenylarsonate antibodies bearing a cross-reactive idiotype. Immunochemistry. 1976 Sep;13(9):783–787. doi: 10.1016/0019-2791(76)90201-9. [DOI] [PubMed] [Google Scholar]
  17. Kearney J. F., Barletta R., Quan Z. S., Quintáns J. Monoclonal vs. heterogeneous anti-H-8 antibodies in the analysis of the anti-phosphorylcholine response in BALB/c mice. Eur J Immunol. 1981 Nov;11(11):877–883. doi: 10.1002/eji.1830111106. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Klinman N. R. The mechanism of antigenic stimulation of primary and secondary clonal precursor cells. J Exp Med. 1972 Aug 1;136(2):241–260. doi: 10.1084/jem.136.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lamoyi E., Estess P., Capra J. D., Nisonoff A. Heterogeneity of an intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice. J Immunol. 1980 Jun;124(6):2834–2840. [PubMed] [Google Scholar]
  21. Lucas A., Henry C. Expression of the major cross-reactive idiotype in a primary anti-azobenzenearsonate response. J Immunol. 1982 Feb;128(2):802–806. [PubMed] [Google Scholar]
  22. Marshak-Rothstein A., Benedetto J. D., Kirsch R. L., Gefter M. L. Unique determinants associated with hybridoma proteins expressing a cross-reactive idiotype: frequency among individual immune sera. J Immunol. 1980 Nov;125(5):1987–1992. [PubMed] [Google Scholar]
  23. Marshak-Rothstein A., Margolies M. N., Benedetto J. D., Gefter M. L. Two structurally distinct and independently regulated idiotypic families associated with the A/J response to azophenylarsonate. Eur J Immunol. 1981 Jul;11(7):565–572. doi: 10.1002/eji.1830110709. [DOI] [PubMed] [Google Scholar]
  24. Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Owen J. A., Sigal N. H., Klinman N. R. Heterogeneity of the BALB/c IgM anti-phosphorylcholine antibody response. Nature. 1982 Jan 28;295(5847):347–348. doi: 10.1038/295347a0. [DOI] [PubMed] [Google Scholar]
  26. Reth M., Imanishi-Kari T., Rajewsky K. Analysis of the repertoire of anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies in C 57 BL/6 mice by cell fusion. II. Characterization of idiotopes by monoclonal anti-idiotope antibodies. Eur J Immunol. 1979 Dec;9(12):1004–1013. doi: 10.1002/eji.1830091216. [DOI] [PubMed] [Google Scholar]
  27. Ruppert V. J., Williams K., Claflin J. L. Specific clonal regulation in the response to phosphocholine. I. Genetic analysis of the response of a distinct idiotype (M511 Id). J Immunol. 1980 Mar;124(3):1068–1074. [PubMed] [Google Scholar]
  28. Sigal N. H., Gearhart P. J., Klinman N. R. The frequency of phosphorylcholine-specific B cells in conventional and germfree BALB/C mice. J Immunol. 1975 Apr;114(4):1354–1358. [PubMed] [Google Scholar]
  29. Sigal N. H., Pickard A. R., Metcalf E. S., Gearhart P. J., Klinman N. R. Expression of phosphorylcholine-specific B cells during murine development. J Exp Med. 1977 Oct 1;146(4):933–948. doi: 10.1084/jem.146.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sigal N. H. The frequency of para-azophenylarsonate and dimethylaminonapthalene-sulfonyl-specific B cells in neonatal and adult BALB/c mice. J Immunol. 1977 Sep;119(3):1129–1133. [PubMed] [Google Scholar]
  31. Stein K. E., Bona C., Lieberman R., Chien C. C., Paul W. E. Regulation of the anti-inulin antibody response by a nonallotype-linked gene. J Exp Med. 1980 May 1;151(5):1088–1102. doi: 10.1084/jem.151.5.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]

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