Abstract
We have previously described an idiotype (Id460) that transiently dominates anti-2,4-dinitrophenyl (DNP) antibody responses of mice that possess the appropriate Igh-V and V kappa genotypes. Normal serum has significant levels of Id460 that does not bind DNP, and hybridomas derived from spleen cell fusions that produce monoclonal antibodies with these characteristics have been generated. Many of these monoclonal, Id460-positive antibodies bind the opportunistic mouse pathogen Pasteurella pneumotropica. P. pneumotropica induces a marked increase in serum Id460 titers without significantly increasing serum anti-DNP titers. Both normal serum and P. pneumotropica-induced Ig460- positive immunoglobulin specifically bind to P. pneumotropica. These results suggest that the normal serum Id460-positive immunoglobulin is induced by environmentally encountered antigens on P. pneumotropica. We propose that this naturally occurring Id460 activates antiidiotypic regulatory cells that in turn promote production of Id460-positive anti- DNP antibody following DNP-ovalbumin immunization. These data are compatible with those obtained in several other idiotypic systems that suggest that dominant idiotypes may be associated with antibodies that have been evolutionarily selected for expression because of their specificity for antigens on environmentally encountered pathogens.
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- Andersson J., Sjöberg O., Möller G. Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur J Immunol. 1972 Aug;2(4):349–353. doi: 10.1002/eji.1830020410. [DOI] [PubMed] [Google Scholar]
- Basta P., Kubagawa H., Kearney J. F., Briles D. E. Ten percent of normal B cells and plasma cells share A VH determinant(s) (J606-GAC) with a distinct subset of murine VHIII plasmacytomas. J Immunol. 1983 May;130(5):2423–2428. [PubMed] [Google Scholar]
- 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]
- Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
- Bottomly K., Janeway C. A., Jr, Mathieson B. J., Mosier D. E. Absence of an antigen-specific helper T cell required for the expression of the T 15 idiotype in mice treated with anti-mu antibody. Eur J Immunol. 1980 Feb;10(2):159–163. doi: 10.1002/eji.1830100217. [DOI] [PubMed] [Google Scholar]
- 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]
- Briles D. E., Davie J. M. Clonal dominance. I. Restricted nature of the IgM antibody response to group A streptococcal carbohydrate in mice. J Exp Med. 1975 Jun 1;141(6):1291–1307. doi: 10.1084/jem.141.6.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Briles D. E., Forman C., Hudak S., Claflin J. L. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J Exp Med. 1982 Oct 1;156(4):1177–1185. doi: 10.1084/jem.156.4.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerny J., Cronkhite R., Heusser C. Antibody response of mice following neonatal treatment with a monoclonal anti-receptor antibody. Evidence for B cell tolerance and T suppressor cells specific for different idiotopic determinants. Eur J Immunol. 1983 Mar;13(3):244–248. doi: 10.1002/eji.1830130313. [DOI] [PubMed] [Google Scholar]
- 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]
- Dzierzak E. A., Janeway C. A., Jr Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. III. Detection of Id-460 in normal serum that does not bind dinitrophenyl. J Exp Med. 1981 Nov 1;154(5):1442–1454. doi: 10.1084/jem.154.5.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dzierzak E. A., Janeway C. A., Jr, Rosenstein R. W., Gottlieb P. D. Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. I. Mapping of genes for Id-460 expression to the variable region of immunoglobulin heavy-chain locus and to the variable region of immunoglobulin kappa-light-chain locus. J Exp Med. 1980 Sep 1;152(3):720–729. doi: 10.1084/jem.152.3.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dzierzak E. A., Rosenstein R. W., Janeway C. A., Jr Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. II. Transient idiotypic dominance. J Exp Med. 1981 Nov 1;154(5):1432–1441. doi: 10.1084/jem.154.5.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichmann K., Coutinho A., Melchers F. Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice. J Exp Med. 1977 Nov 1;146(5):1436–1449. doi: 10.1084/jem.146.5.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hetzelberger D., Eichmann K. Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes. Eur J Immunol. 1978 Dec;8(12):846–852. doi: 10.1002/eji.1830081205. [DOI] [PubMed] [Google Scholar]
- Hornbeck P. V., Lewis G. K. Idiotype connectance in the immune system. I. Expression of a cross-reactive idiotype on induced anti-p-azophenylarsonate antibodies and on endogenous antibodies not specific for arsonate. J Exp Med. 1983 Apr 1;157(4):1116–1136. doi: 10.1084/jem.157.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imanishi T., Mäkelä O. Inheritance of antibody specificity. I. Anti-(4-hydroxy-3-nitrophenyl)acetyl of the mouse primary response. J Exp Med. 1974 Dec 1;140(6):1498–1510. doi: 10.1084/jem.140.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JAWETZ E. A pneumotropic pasteurella of laboratory animals; bacteriological and serological characteristics of the organism. J Infect Dis. 1950 Mar-Apr;86(2):172–183. doi: 10.1093/infdis/86.2.172. [DOI] [PubMed] [Google Scholar]
- Jakab G. J., Dick E. C. Synergistic effect in viral-bacterial infection: combined infection of the murine respiratory tract with Sendai virus and Pasteurella pneumotropica. Infect Immun. 1973 Nov;8(5):762–768. doi: 10.1128/iai.8.5.762-768.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janeway C. A., Jr, Murgita R. A., Weinbaum F. I., Asofsky R., Wigzell H. Evidence for an immunoglobulin-dependent antigen-specific helper T cell. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4582–4586. doi: 10.1073/pnas.74.10.4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
- Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
- Kelsoe G., Isaak D., Cerny J. Thymic requirement for cyclical idiotypic and reciprocal anti-idiotypic immune responses to a T-independent antigen. J Exp Med. 1980 Feb 1;151(2):289–300. doi: 10.1084/jem.151.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lieberman R., Potter M., Humphrey W., Jr, Chien C. C. Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse. J Immunol. 1976 Dec;117(6):2105–2111. [PubMed] [Google Scholar]
- 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]
- Nisonoff A., Ju S. T., Owen F. L. Studies of structure and immunosuppression of cross-reactive idiotype in strain A mice. Immunol Rev. 1977;34:89–118. doi: 10.1111/j.1600-065x.1977.tb00369.x. [DOI] [PubMed] [Google Scholar]
- Potter M. Antigen-binding myeloma proteins in mice. Ann N Y Acad Sci. 1971 Dec 31;190:306–321. doi: 10.1111/j.1749-6632.1971.tb13543.x. [DOI] [PubMed] [Google Scholar]
- Sercarz E. E., Metzger D. W. Epitope-specific and idiotype-specific cellular interactions in a model protein antigen system. Springer Semin Immunopathol. 1980 Aug;3(2):145–170. doi: 10.1007/BF02053974. [DOI] [PubMed] [Google Scholar]
- Smith P. B., Tomfohrde K. M., Rhoden D. L., Balows A. API system: a multitube micromethod for identification of Enterobacteriaceae. Appl Microbiol. 1972 Sep;24(3):449–452. doi: 10.1128/am.24.3.449-452.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stohrer R., Lee M. C., Kearney J. F. Analysis of the anti-alpha 1 leads to 3 dextran response with monoclonal anti-idiotype antibodies. J Immunol. 1983 Sep;131(3):1375–1379. [PubMed] [Google Scholar]
- Takemori T., Tesch H., Reth M., Rajewsky K. The immune response against anti-idiotope antibodies. I. Induction of idiotope-bearing antibodies and analysis of the idiotope repertoire. Eur J Immunol. 1982 Dec;12(12):1040–1046. doi: 10.1002/eji.1830121210. [DOI] [PubMed] [Google Scholar]
- Urbain J., Wuilmart C., Cazenave P. A. Idiotypic regulation in immune networks. Contemp Top Mol Immunol. 1981;8:113–148. doi: 10.1007/978-1-4684-3917-5_4. [DOI] [PubMed] [Google Scholar]
- 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]
- Wysocki L. J., Sato V. L. The strain A anti-p-azophenylarsonate major cross-reactive idiotypic family includes members with no reactivity toward p-azophenylarsonate. Eur J Immunol. 1981 Oct;11(10):832–839. doi: 10.1002/eji.1830111016. [DOI] [PubMed] [Google Scholar]