Abstract
The idiotypic (Id) diversity of the immune response to phosphorylcholine (PC) was studied by immunization of mice with thymus-dependent (PC-keyhole limpet haemocyanin; PC-KLH) and thymus-independent (S. pneumoniae R36a; Pn) forms of the antigen. Mice with the BALB/c genetic background (BALB/c, C.B20, and BALB.B) were used because their response to PC is dominated by immunoglobulins encoded in VH-1 and V kappa 22 genes, which uniformly express the T15 idiotype. The actual repertoire of the antibody was determined by idiotypic markers (Id) defined with monoclonal antibodies designated AB1-2, B36-82, MaId5-4, and B24-44. Previous studies from our laboratory have shown that these Id are present on T15 (VS107-1/V kappa 22) immunoglobulins only, but that they differentiate between somatic variants of the antibody molecules. We have measured the serum concentrations of these four Id after primary (1 degree), secondary (2 degree), and tertiary (3 degree) immunization; all of the Id activity was associated with the PC-binding antibody, as shown by specific immunoadsorbents. However, the levels of the Id-bearing (Id+) antibody did not correlate with each other. After immunization with PC-KLH, the AB1-2+ antibody declined precipitously, whereas the levels of B24-44 and B36-82 remained steady. A similar pattern of Id heterogeneity was seen at the level of direct antibody-plaque-forming cells from the spleen, suggesting that the idiotopic (clonal) diversification occurred already during the early IgM response. A significant portion of anti-PC antibody after the 3 degrees PC-KLH immunization was negative for all four Id, implying that the late response to the antigen involved distinct, T15-negative clones.
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Selected References
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- 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]
- Cerny J., Cronkhite R., Stout J. T. Rapid changes in the regulatory potential of autologous anti-idiotopic T cells during an antigen-driven primary response. J Immunol. 1986 May 15;136(10):3597–3606. [PubMed] [Google Scholar]
- Chang S. P., Brown M., Rittenberg M. B. Immunologic memory to phosphorylcholine III. IgM includes a fine specificity population distinct from TEPC 15. J Immunol. 1982 Oct;129(4):1559–1562. [PubMed] [Google Scholar]
- Chang S. P., Brown M., Rittenberg M. B. Immunologic memory to phosphorylcholine. II. PC-KLH induces two antibody populations that dominate different isotypes. J Immunol. 1982 Feb;128(2):702–706. [PubMed] [Google Scholar]
- Chang S. P., Perlmutter R. M., Brown M., Heusser C. H., Hood L., Rittenberg M. B. Immunologic memory to phosphocholine. IV. Hybridomas representative of Group I (T15-like) and Group II (non-T15-like) antibodies utilize distinct VH genes. J Immunol. 1984 Mar;132(3):1550–1555. [PubMed] [Google Scholar]
- Chang S. P., Rittenberg M. B. Immunologic memory to phosphorylcholine in vitro. I. Asymmetric expression of clonal dominance. J Immunol. 1981 Mar;126(3):975–980. [PubMed] [Google Scholar]
- Claflin J. L., Cubberley M. Clonal nature of the immune response to phosphocholine. VII. Evidence throughout inbred mice for molecular similarities among antibodies bearing the T15 idiotype. J Immunol. 1980 Aug;125(2):551–558. [PubMed] [Google Scholar]
- Cronkhite R., Strickland F., Cerny J. Regulation of idiotope expression. III. H-2 influences the magnitude and the idiotypy of a T-independent antibody response in mice of certain genetic backgrounds. J Immunol. 1988 Aug 1;141(3):921–925. [PubMed] [Google Scholar]
- Cuatrecasas P. Protein purification by affinity chromatography. Derivatizations of agarose and polyacrylamide beads. J Biol Chem. 1970 Jun;245(12):3059–3065. [PubMed] [Google Scholar]
- Davie J. M., Seiden M. V., Greenspan N. S., Lutz C. T., Bartholow T. L., Clevinger B. L. Structural correlates of idiotopes. Annu Rev Immunol. 1986;4:147–165. doi: 10.1146/annurev.iy.04.040186.001051. [DOI] [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]
- GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Greenspan N. S., Fulton R. J., Davie J. M. Analysis of anti-streptococcal group A carbohydrate idiotope levels in sera: correlation of magnitude of expression with idiotope position and VK haplotype. J Immunol. 1986 Jul 1;137(1):228–233. [PubMed] [Google Scholar]
- Inman J. K., Merchant B., Tacey S. E. Synthesis of large haptenic compounds having a common functional group that permits covalent linkage to proteins, cell surfaces, and adsorbents. Immunochemistry. 1973 Mar;10(3):153–163. doi: 10.1016/0019-2791(73)90004-9. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Kim J., Woods A., Becker-Dunn E., Bottomly K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J Exp Med. 1985 Jul 1;162(1):188–201. doi: 10.1084/jem.162.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunkel H. G., Mannik M., Williams R. C. Individual Antigenic Specificity of Isolated Antibodies. Science. 1963 Jun 14;140(3572):1218–1219. doi: 10.1126/science.140.3572.1218. [DOI] [PubMed] [Google Scholar]
- Köhler H. The response to phosphorylcholine: dissecting an immune response. Transplant Rev. 1975;27:24–56. [PubMed] [Google Scholar]
- 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]
- Perlmutter R. M., Crews S. T., Douglas R., Sorensen G., Johnson N., Nivera N., Gearhart P. J., Hood L. The generation of diversity in phosphorylcholine-binding antibodies. Adv Immunol. 1984;35:1–37. doi: 10.1016/s0065-2776(08)60572-6. [DOI] [PubMed] [Google Scholar]
- Reth M., Hämmerling G. J., Rajewsky K. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur J Immunol. 1978 Jun;8(6):393–400. doi: 10.1002/eji.1830080605. [DOI] [PubMed] [Google Scholar]
- Rubin A. S., Coons A. H. Specific heterologous enhancement of immune responses. 3. Partial characterization of supernatant material with enhancing activity. J Immunol. 1972 Jun;108(6):1597–1604. [PubMed] [Google Scholar]
- Steward M. W., Lew A. M. The importance of antibody affinity in the performance of immunoassays for antibody. J Immunol Methods. 1985 Apr 22;78(2):173–190. doi: 10.1016/0022-1759(85)90074-2. [DOI] [PubMed] [Google Scholar]
- Stout J. T., Strickland F. M., Cerny J. Regulation of idiotope expression. I. The effect of antigen dose on expression of certain T15 idiotopes during primary IgM response to S. pneumoniae R36a. J Immunol. 1985 Mar;134(3):1926–1929. [PubMed] [Google Scholar]
- Strickland F. M., Gleason J. T., Cerny J. Serologic and molecular characterization of the T15 idiotype--I. Topologic mapping of idiotopes on TEPC15. Mol Immunol. 1987 Jun;24(6):631–635. doi: 10.1016/0161-5890(87)90044-7. [DOI] [PubMed] [Google Scholar]
- Strickland F. M., Gleason J. T., Cerny J. Serologic and molecular characterization of the T15 idiotype--II. Structural basis of independent idiotope expression on phosphorylcholine-specific monoclonal antibodies. Mol Immunol. 1987 Jun;24(6):637–646. doi: 10.1016/0161-5890(87)90045-9. [DOI] [PubMed] [Google Scholar]
- Todd I., Brown M., Rittenberg M. B. Immunologic memory to phosphorylcholine. VI. Heterogeneity in light chain gene expression. Eur J Immunol. 1985 Feb;15(2):177–183. doi: 10.1002/eji.1830150213. [DOI] [PubMed] [Google Scholar]
- Todd I., Chang S. P., Perlmutter R. M., Aebersold R., Heusser C. H., Hood L., Rittenberg M. B. Immunologic memory to phosphocholine. V. Hybridomas representative of group II antibodies utilize V kappa 1-3 gene(s). J Immunol. 1984 Mar;132(3):1556–1560. [PubMed] [Google Scholar]
- Wicker L. S., Guelde G., Scher I., Kenny J. J. The asymmetry in idiotype-isotype expression in the response to phosphocholine is due to divergence in the expressed repertoires of Lyb-5+ and Lyb-5- B cells. J Immunol. 1983 Nov;131(5):2468–2476. [PubMed] [Google Scholar]
