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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Oct 15;90(20):9508–9512. doi: 10.1073/pnas.90.20.9508

Molecular characterization of monoclonal CRIA-positive anti-arsonate antibodies derived from idiotype-negative mice bearing a light chain polymorphism.

J Tassignon 1, M Brait 1, J Ismaili 1, J Urbain 1, P Gottlieb 1, A Brown 1, C A Hasemann 1, J D Capra 1, K Meek 1
PMCID: PMC47598  PMID: 8415731

Abstract

We have elicited anti-arsonate antibodies bearing the major cross-reactive idiotype (CRIA) in a double congenic idiotype-negative strain (C.C58.AL-20) bearing a light chain polymorphism that has previously been shown serologically not to complement idiotype-positive heavy chains. Using the idiotype cascade (Ab1-->Ab2-->Ab3-->-->Ab1'), CRIA-positive antibodies were raised and monoclonal antibodies were isolated and characterized serologically and by nucleotide sequence analysis. Two types of idiotype-positive anti-arsonate antibodies were generated in the C.C58.AL-20 strain. One group of hybridomas used the canonical VH1.8 heavy chain gene segment with V kappa 10 variant light chains. A second group used a VHGAM3.8 heavy chain with V kappa 10 variant light chains. This latter heavy-light pairing has been observed in CRIA-like responses previously in BALB/c mice after idiotypic manipulation (or rarely after antigen alone). These studies demonstrate the plasticity of the immune response when manipulated with idiotype reagents as well as its structural variability. Additionally, they provide important insights into the potentials of idiotype vaccines.

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Selected References

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  1. Bona C. A. Expression of V gene families during ontogeny and establishment of B cell repertoire. Int Rev Immunol. 1992;8(2-3):83–94. doi: 10.3109/08830189209055565. [DOI] [PubMed] [Google Scholar]
  2. Brown A. R., Gottlieb P. D. BALB/c antiarsonate idiotypes: gene complementation necessary for expression. Immunogenetics. 1984;20(4):417–432. doi: 10.1007/BF00345616. [DOI] [PubMed] [Google Scholar]
  3. Brown A. R., Gottlieb P. D., Nisonoff A. Role and strain distribution of genes controlling light chains needed for the expression of an intrastrain cross-reactive idiotype. Immunogenetics. 1981;14(1-2):85–99. doi: 10.1007/BF00344302. [DOI] [PubMed] [Google Scholar]
  4. Cazenave P. A. Idiotypic-anti-idiotypic regulation of antibody synthesis in rabbits. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5122–5125. doi: 10.1073/pnas.74.11.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gibson D. M., Taylor B. A., Cherry M. Evidence for close linkage of a mouse light chain marker with the Ly-2,3 locus. J Immunol. 1978 Oct;121(4):1585–1590. [PubMed] [Google Scholar]
  6. Gibson D. Genetic polymorphism of mouse immunoglobulin light chains revealed by isoelectric focusing. J Exp Med. 1976 Jul 1;144(1):298–303. doi: 10.1084/jem.144.1.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldrick M. M., Boyd R. T., Ponath P. D., Lou S. Y., Gottlieb P. D. Molecular genetic analysis of the V kappa Ser group associated with two mouse light chain genetic markers. Complementary DNA cloning and southern hybridization analysis. J Exp Med. 1985 Aug 1;162(2):713–728. doi: 10.1084/jem.162.2.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haba S., Lascombe M. B., Poljak R. J., Nisonoff A. Structure of idiotopes associated with antiphenylarsonate antibodies expressing an intrastrain crossreactive idiotype. J Exp Med. 1989 Oct 1;170(4):1075–1090. doi: 10.1084/jem.170.4.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hasemann C. A., Capra J. D. Mutational analysis of the cross-reactive idiotype of the A strain mouse. J Immunol. 1991 Nov 1;147(9):3170–3179. [PubMed] [Google Scholar]
  10. Hornbeck P. V., Lewis G. K. Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p-azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group. J Exp Med. 1985 Jan 1;161(1):53–71. doi: 10.1084/jem.161.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jeske D., Milner E. C., Leo O., Moser M., Marvel J., Urbain J., Capra J. D. Molecular mapping of idiotopes of anti-arsonate antibodies. J Immunol. 1986 Apr 1;136(7):2568–2574. [PubMed] [Google Scholar]
  12. Kaartinen M., Griffiths G. M., Markham A. F., Milstein C. mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification. 1983 Jul 28-Aug 3Nature. 304(5924):320–324. doi: 10.1038/304320a0. [DOI] [PubMed] [Google Scholar]
  13. Kim S. O., Sanz I., Williams C., Capra J. D., Gottlieb P. D. Polymorphism in V kappa 10 genes encoding L chains of antibodies bearing the Ars-A and A48 cross-reactive idiotypes. Immunogenetics. 1991;34(4):231–241. doi: 10.1007/BF00215258. [DOI] [PubMed] [Google Scholar]
  14. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kurosawa Y., Tonegawa S. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med. 1982 Jan 1;155(1):201–218. doi: 10.1084/jem.155.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lafaille J. J., DeCloux A., Bonneville M., Takagaki Y., Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell. 1989 Dec 1;59(5):859–870. doi: 10.1016/0092-8674(89)90609-0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Margolies M. N., Marshak-Rothstein A., Gefter M. L. Structural diversity among anti-p-azophenylarsonate monoclonal antibodies from A/J mice; comparison of Id- and Id+ sequences. Mol Immunol. 1981 Dec;18(12):1065–1077. doi: 10.1016/0161-5890(81)90022-5. [DOI] [PubMed] [Google Scholar]
  20. Marvel J., Tassignon J., Brait M., Meek K., Milner E. C., Moser M., Capra J. D., Urbain J. The influence of V kappa gene polymorphism on the induction of silent idiotypes in the arsonate system. Mol Immunol. 1987 May;24(5):463–469. doi: 10.1016/0161-5890(87)90020-4. [DOI] [PubMed] [Google Scholar]
  21. Meek K., Hasemann C., Pollok B., Alkan S. S., Brait M., Slaoui M., Urbain J., Capra J. D. Structural characterization of antiidiotypic antibodies. Evidence that Ab2s are derived from the germline differently than Ab1s. J Exp Med. 1989 Feb 1;169(2):519–533. doi: 10.1084/jem.169.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Meek K., Sanz I., Rathbun G., Nisonoff A., Capra J. D. Identity of the V kappa 10-Ars-A gene segments of the A/J and BALB/c strains. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6244–6248. doi: 10.1073/pnas.84.17.6244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pawlak L. L., Mushinski E. B., Nisonoff A., Potter M. Evidence for the linkage of the IGC H locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice. J Exp Med. 1973 Jan 1;137(1):22–31. doi: 10.1084/jem.137.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rathbun G. A., Otani F., Milner E. C., Capra J. D., Tucker P. W. Molecular characterization of the A/J J558 family of heavy chain variable region gene segments. J Mol Biol. 1988 Aug 5;202(3):383–395. doi: 10.1016/0022-2836(88)90272-0. [DOI] [PubMed] [Google Scholar]
  26. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanz I., Capra J. D. V kappa and J kappa gene segments of A/J Ars-A antibodies: somatic recombination generates the essential arginine at the junction of the variable and joining regions. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1085–1089. doi: 10.1073/pnas.84.4.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sharon J., Gefter M. L., Manser T., Ptashne M. Site-directed mutagenesis of an invariant amino acid residue at the variable-diversity segments junction of an antibody. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2628–2631. doi: 10.1073/pnas.83.8.2628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Siegelman M., Capra J. D. Complete amino acid sequence of light chain variable regions derived from five monoclonal anti-p-azophenylarsonate antibodies differing with respect to a crossreactive idiotype. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7679–7683. doi: 10.1073/pnas.78.12.7679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Siekevitz M., Gefter M. L., Brodeur P., Riblet R., Marshak-Rothstein A. The genetic basis of antibody production: the dominant anti-arsonate idiotype response of the strain A mouse. Eur J Immunol. 1982 Dec;12(12):1023–1032. doi: 10.1002/eji.1830121208. [DOI] [PubMed] [Google Scholar]
  32. Sims M. J., Krawinkel U., Taussig M. J. Characterization of germ-line genes of the VGAM3.8 VH gene family from BALB/c mice. J Immunol. 1992 Sep 1;149(5):1642–1648. [PubMed] [Google Scholar]
  33. Slaughter C. A., Jeske D. J., Kuziel W. A., Milner E. C., Capra J. D. Use of JH4 joining segment gene by an anti-arsonate antibody that bears the major A-strain cross-reactive idiotype but displays diminished antigen binding. J Immunol. 1984 Jun;132(6):3164–3171. [PubMed] [Google Scholar]
  34. Urbain J., Wikler M., Franssen J. D., Collignon C. Idiotypic regulation of the immune system by the induction of antibodies against anti-idiotypic antibodies. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5126–5130. doi: 10.1073/pnas.74.11.5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wysocki L. J., Manser T., Gridley T., Gefter M. L. Molecular limitations on variable-gene junctional diversity. J Immunol. 1986 Dec 15;137(12):3699–3701. [PubMed] [Google Scholar]
  36. Yang J. N., Dudley J. Endogenous Mtv-8 or a closely linked sequence stimulates rearrangement of the downstream V kappa 9 gene. J Immunol. 1992 Aug 15;149(4):1242–1251. [PubMed] [Google Scholar]
  37. Zaghouani H., Bonilla F. A., Meek K., Bona C. Molecular basis for expression of the A48 regulatory idiotope on antibodies encoded by immunoglobulin variable-region genes from various families. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2341–2345. doi: 10.1073/pnas.86.7.2341. [DOI] [PMC free article] [PubMed] [Google Scholar]

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