Abstract
The maturation of the antibody response to phosphorylcholine (PC) in neonatal BALB/c mice was studied. A T cell-independent class 1 1 PC- antigen, 3-(p-azophenyl phosphorylcholine)-N-acetyl-L- tyrosylglycylglycine lipopolysaccharide, was synthesized and used to immunize neonatal mice of different ages. The earliest anti-PC hemolytic plaque-forming response could be induced in 1-d-old neonates. Idiotype analysis on these early anti-PC antibodies showed that the response was not TEPC-15 dominant although TEPC-15-positive plaque- forming cells were detected. However, idiotype analysis of the anti-PC- LPS response in 7 d or older animals indicated that clonal dominance had been established. Similar results were obtained in splenic fragment culture with cells from neonatal livers and spleens. PC-specific precursors were detected in the liver of 1-d-old neonates, whereas the spleen of those animals contained no precursors for PC. Precursors for PC residing in the neonatal liver are not TEPC-15 dominant, whereas the splenic PC precursors of 5- to 6-day-old animals express the TEPC-15 idiotype dominatly. These findings demonstrate that during ontogeny PC- specific B cells appear before the TEPC-15 clone becomes dominant. Thus clonal dominance in the adult anti-PC response and late acquisition of the TEPC-15 specificity during ontogeny do not signify a particularly unique or direct relationship to the expression of genes encoded in the germline.
Full Text
The Full Text of this article is available as a PDF (795.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- Bottomly K., Mathieson B. J., Mosier D. E. Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice. J Exp Med. 1978 Nov 1;148(5):1216–1227. doi: 10.1084/jem.148.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesebro B., Metzger H. Affinity labeling of a phosphorylcholine binding mouse myeloma protein. Biochemistry. 1972 Feb 29;11(5):766–771. doi: 10.1021/bi00755a014. [DOI] [PubMed] [Google Scholar]
- Chiller J. M., Skidmore B. J., Morrison D. C., Weigle W. O. Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2129–2133. doi: 10.1073/pnas.70.7.2129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Claflin J. L., Cubberley M. Clonal nature of the immune response to phosphocholine. VI. Molecular uniformity of a single idiotype among BALB/c mice. J Immunol. 1978 Oct;121(4):1410–1415. [PubMed] [Google Scholar]
- Cooper M. D., Lawton A. R., 3rd The development of the immune system. Sci Am. 1974 Nov;231(5):58–72. doi: 10.1038/scientificamerican1174-58. [DOI] [PubMed] [Google Scholar]
- Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
- Eichmann K., Berek C. Mendelian segregation of a mouse antibody idiotype. Eur J Immunol. 1973 Sep;3(9):599–601. doi: 10.1002/eji.1830030914. [DOI] [PubMed] [Google Scholar]
- Eichmann K. Idiotype expression and the inheritance of mouse antibody clones. J Exp Med. 1973 Mar 1;137(3):603–621. doi: 10.1084/jem.137.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichmann K. Idiotype suppression. I. Influence of the dose and of the effector functions of anti-idiotypic antibody on the production of an idiotype. Eur J Immunol. 1974 Apr;4(4):296–302. doi: 10.1002/eji.1830040413. [DOI] [PubMed] [Google Scholar]
- Eichmann K., Rajewsky K. Induction of T and B cell immunity by anti-idiotypic antibody. Eur J Immunol. 1975 Oct;5(10):661–666. doi: 10.1002/eji.1830051002. [DOI] [PubMed] [Google Scholar]
- Etlinger H. M., Chiller J. M. Maturation of the lymphoid system. II. Characterization of the cellular levels of unresponsiveness induced in neonates by a T-dependent antigen that is an obligate immunogen in adults. J Immunol. 1979 Jun;122(6):2564–2570. [PubMed] [Google Scholar]
- Fidler J. M. In vivo immune response to TNP hapten coupled to thymus-independent carrier lipopolysaccharide. Cell Immunol. 1975 Apr;16(2):223–236. doi: 10.1016/0008-8749(75)90114-8. [DOI] [PubMed] [Google Scholar]
- Fidler J. M. The induction of hapten-specific immunological tolerance and immunity in B lymphocytes. VI. Differential tolerance susceptibility in adult spleen as a function of B-cell maturation level. J Exp Med. 1979 Sep 19;150(3):491–506. doi: 10.1084/jem.150.3.491. [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]
- Gold E. R., Fudenberg H. H. Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol. 1967 Nov;99(5):859–866. [PubMed] [Google Scholar]
- Inman J. K., Merchant B., Claflin L., Tacey S. E. Coupling of large haptens to proteins and cell surfaces: preparation of stable, optimally sensitized erythrocytes for hapten-specific, hemolytic plaque assays. Immunochemistry. 1973 Mar;10(3):165–174. doi: 10.1016/0019-2791(73)90005-0. [DOI] [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]
- Julius M. H., Cosenza H., Augustin A. A. Evidence for the endogenous production of T cell receptors bearing idiotypic determinants. Eur J Immunol. 1978 Jul;8(7):484–491. doi: 10.1002/eji.1830080707. [DOI] [PubMed] [Google Scholar]
- Kaplan D. R., Quintans J., Köhler H. Clonal dominance: loss and restoration in adoptive transfer. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1967–1970. doi: 10.1073/pnas.75.4.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klinman N. R., Press J. L. The B cell specificity repertoire: its relationship to definable subpopulations. Transplant Rev. 1975;24:41–83. doi: 10.1111/j.1600-065x.1975.tb00165.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Klinman N. R. The secondary immune response to a hapten in vitro. Antigen concentration and the carrier effect. J Exp Med. 1971 May 1;133(5):963–972. doi: 10.1084/jem.133.5.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Köhler H., Fung J., Smyk S. Induced recovery of a suppressed idiotype by immunization with anti-idiotype. Cell Immunol. 1980 Jul 1;52(2):458–463. doi: 10.1016/0008-8749(80)90367-6. [DOI] [PubMed] [Google Scholar]
- Köhler H., Kaplan D. R., Strayer D. S. Clonal depletion in neonatal tolerance. Science. 1974 Nov 15;186(4164):643–644. doi: 10.1126/science.186.4164.643. [DOI] [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]
- McKearn J. P., Quintáns J. Delineation of tolerance-sensitive and tolerance-insensitive B cells in normal and immune defective mice. J Immunol. 1980 Jan;124(1):77–80. [PubMed] [Google Scholar]
- McKearn J. P., Quintáns J. Ontogeny of murine B-cell responses to thymus-independent trinitrophenyl antigens. Cell Immunol. 1979 May;44(2):367–380. doi: 10.1016/0008-8749(79)90012-1. [DOI] [PubMed] [Google Scholar]
- McKenzie I. F., Potter T. Murine lymphocyte surface antigens. Adv Immunol. 1979;27:179–338. doi: 10.1016/s0065-2776(08)60263-1. [DOI] [PubMed] [Google Scholar]
- Merchant B., Snippe H., Lizzio E. F., Inman J. K. X-linked genetic control of hapten-polysaccharide-mediated specific immune unresponsiveness in CBA/N mice. J Immunol. 1978 Apr;120(4):1362–1368. [PubMed] [Google Scholar]
- Mosier D. E., Mond J. J., Goldings E. A. The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect. J Immunol. 1977 Dec;119(6):1874–1878. [PubMed] [Google Scholar]
- Natali P. G., Cioli D. Immune complex nephritis in Schistosoma mansoni-infected mice. Eur J Immunol. 1976 May;6(5):359–364. doi: 10.1002/eji.1830060511. [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]
- Potter M., Lieberman R. Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline. J Exp Med. 1970 Oct 1;132(4):737–751. doi: 10.1084/jem.132.4.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quintáns J., McKearn J. P., Kaplan D. B cell heterogeneity. I. A study of B cell subpopulations involved in the reconstitution of an X-linked immune defect of B cell differentiation. J Immunol. 1979 May;122(5):1750–1756. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strayer D. S., Lee W. M., Rowley D. A., Köhler H. Anti-receptor antibody. II. Induction of long-term unresponsiveness in neonatal mice. J Immunol. 1975 Feb;114(2 Pt 2):728–733. [PubMed] [Google Scholar]
- Teale J. M., Howard M. C., Falzon E., Nossal G. J. B lymphocyte subpopulations separated by velocity sedimentation. I. Characterization of immune function in an in vitro splenic focus assay. J Immunol. 1978 Dec;121(6):2554–2560. [PubMed] [Google Scholar]
- Teale J. M., Howard M. C., Nossal G. J. B lymphocyte subpopulations separated by velocity sedimentation. II. Characterization of tolerance susceptibility. J Immunol. 1978 Dec;121(6):2561–2565. [PubMed] [Google Scholar]
- Teale J. M., Mandel T. E. Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system. J Exp Med. 1980 Feb 1;151(2):429–445. doi: 10.1084/jem.151.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]