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. 1977 Oct 1;146(4):933–948. doi: 10.1084/jem.146.4.933

Expression of phosphorylcholine-specific B cells during murine development

NH Sigal, AR Pickard, ES Metcalf, PJ Gearhart, NR Klinman
PMCID: PMC2180820  PMID: 302315

Abstract

The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen. These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated.

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Selected References

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  1. Argyris B. F. Role of macrophages in immunological maturation. J Exp Med. 1968 Sep 1;128(3):459–467. doi: 10.1084/jem.128.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arrenbrecht S. Normal development of the thymus-dependent limb of humoral immune responses in mice. Eur J Immunol. 1973 Aug;3(8):506–511. doi: 10.1002/eji.1830030811. [DOI] [PubMed] [Google Scholar]
  3. Braun D. G., Quintáns J., Luzzati A. L., Lefkovits I., Read S. E. Antibody response of rabbit blood lymphocytes in vitro. Kinetics, clone size, and clonotype analysis in response to streptococcal group polysaccharide antigens. J Exp Med. 1976 Feb 1;143(2):360–371. doi: 10.1084/jem.143.2.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chiscon M. Q., Golub E. S. Functional development of the interacting cells in the immune response. I. Development of T cell and B cell function. J Immunol. 1972 May;108(5):1379–1386. [PubMed] [Google Scholar]
  5. Claflin J. L., Lieberman R., Davie J. M. Clonal nature of the immune response to phosphorylcholine. I. Specificity, class, and idiotype of phosphorylcholine-binding receptors on lymphoid cells. J Exp Med. 1974 Jan 1;139(1):58–73. doi: 10.1084/jem.139.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claflin J. L., Rudikoff S. Uniformity in a clonal repertoire: a case for a germ-line basis of antibody diversity. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):725–734. doi: 10.1101/sqb.1977.041.01.083. [DOI] [PubMed] [Google Scholar]
  7. Cosenza H., Quintáns J., Lefkovits I. Antibody response to phosphorylcholine in vitro. I. Studies on the frequency of precursor cells, average clone size and cellular cooperation. Eur J Immunol. 1975 May;5(5):343–349. doi: 10.1002/eji.1830050510. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. D'Eustachio P., Cohen J. E., Edelman G. M. Variation and control of specific antigen-binding cell populations in individual fetal mice. J Exp Med. 1976 Jul 1;144(1):259–265. doi: 10.1084/jem.144.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. D'Eustachio P., Edelman G. M. Frequency and avidity of specific antigen-binding cells in developing mice. J Exp Med. 1975 Nov 1;142(5):1078–1091. doi: 10.1084/jem.142.5.1078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davie J. M., Paul W. E. Antigen-binding receptors on lymphocytes. Contemp Top Immunobiol. 1974;3:171–192. doi: 10.1007/978-1-4684-3045-5_7. [DOI] [PubMed] [Google Scholar]
  12. Decker J. M., Clarke J., Bradley L. M., Miller A., Sercarz E. E. Presence of antigen-binding cells for five diverse antigens at the onset of lymphoid development: lack of evidence for somatic diversification during ontogeny. J Immunol. 1974 Dec;113(6):1823–1833. [PubMed] [Google Scholar]
  13. 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]
  14. Gearhart P. J., Sigal N. H., Klinman N. R. The monoclonal anti-phosphorylcholine antibody response in several murine strains: genetic implications of a diverse repertoire. J Exp Med. 1977 Apr 1;145(4):876–891. doi: 10.1084/jem.145.4.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gelfand M. C., Elfenbein G. J., Frank M. M., Paul W. E. Ontogeny of B lymphocytes. II. Relative rates of appearance of lymphocytes bearing surface immunoglobulin and complement receptors. J Exp Med. 1974 May 1;139(5):1125–1141. doi: 10.1084/jem.139.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goidl E. A., Siskind G. W. Ontogeny of B-lymphocyte function. I. Restricted heterogeneity of the antibody response of B lymphocytes from neonatal and fetal mice. J Exp Med. 1974 Nov 1;140(5):1285–1302. doi: 10.1084/jem.140.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  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., 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]
  20. Klinman N. R., Press J. L. The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice. J Exp Med. 1975 May 1;141(5):1133–1146. doi: 10.1084/jem.141.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Landahl C. A. Ontogeny of adherent cells. I. Distribution and ontogeny of A cells participating in the response to sheep erythrocytes in vitro. Eur J Immunol. 1976 Feb;6(2):130–134. doi: 10.1002/eji.1830060212. [DOI] [PubMed] [Google Scholar]
  23. Lieberman R., Humphrey W., Jr Association of H-2 types with genetic control of immune responsiveness to IgA allotypes in the mouse. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2510–2513. doi: 10.1073/pnas.68.10.2510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Metcalf E. S., Sigal N. H., Klinman N. R. In vitro tolerance induction of neonatal murine B cells as a probe for the study of B-cell diversification. J Exp Med. 1977 May 1;145(5):1382–1386. doi: 10.1084/jem.145.5.1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mäkelä O., Karjalainen K. Inherited immunoglobulin idiotypes of the mouse. Immunol Rev. 1977;34:119–138. doi: 10.1111/j.1600-065x.1977.tb00370.x. [DOI] [PubMed] [Google Scholar]
  27. Nossal G. J., Pike B. L. Studies on the differentiation of B lymphocytes in the mouse. Immunology. 1973 Jul;25(1):33–45. [PMC free article] [PubMed] [Google Scholar]
  28. Owen J. J., Raff M. C., Cooper M. D. Studies on the generation of B lymphocytes in the mouse embryo. Eur J Immunol. 1976 Jul;5(7):468–473. doi: 10.1002/eji.1830050708. [DOI] [PubMed] [Google Scholar]
  29. Pink J. R., Askonas B. A. Diversity of antibodies to cross-reacting nitrophenyl haptens in inbred mice. Eur J Immunol. 1974 Jun;4(6):426–430. doi: 10.1002/eji.1830040608. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Press J. L., Klinman N. R. Enumeration and analysis of antibody-forming cell precursors in the neonatal mouse. J Immunol. 1973 Sep;111(3):829–835. [PubMed] [Google Scholar]
  32. Press J. L., Klinman N. R. Frequency of hapten-specific B cells in neonatal and adult murine spleens. Eur J Immunol. 1974 Mar;4(3):155–159. doi: 10.1002/eji.1830040302. [DOI] [PubMed] [Google Scholar]
  33. Press J. L., Klinman N. R. Isoelectric analysis of neonatal monofocal antibody. Immunochemistry. 1973 Sep;10(9):621–627. doi: 10.1016/0019-2791(73)90164-x. [DOI] [PubMed] [Google Scholar]
  34. SILVERSTEIN A. M., UHR J. W., KRANER K. L., LUKES R. J. Fetal response to antigenic stimulus. II. Antibody production by the fetal lamb. J Exp Med. 1963 May 1;117:799–812. doi: 10.1084/jem.117.5.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sher A., Cohn M. Inheritance of an idiotype associated with the immune response of inbred mice to phosphorylcholine. Eur J Immunol. 1972 Aug;2(4):319–326. doi: 10.1002/eji.1830020405. [DOI] [PubMed] [Google Scholar]
  36. Sherwin W. K., Rowlands D. T., Jr Determinants of the hierarchy of humoral immune responsiveness during ontogeny. J Immunol. 1975 Dec;115(6):1549–1554. [PubMed] [Google Scholar]
  37. Sidman C. L., Unanue E. R. Development of B lymphocytes. I. Cell populations and a critical event during ontogeny. J Immunol. 1975 Jun;114(6):1730–1735. [PubMed] [Google Scholar]
  38. 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]
  39. Spear P. G., Edelman G. M. Maturation of the humoral immune response in mice. J Exp Med. 1974 Feb 1;139(2):249–263. doi: 10.1084/jem.139.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Spear P. G., Wang A. L., Rutishauser U., Edelman G. M. Characterization of splenic lymphoid cells in fetal and newborn mice. J Exp Med. 1973 Sep 1;138(3):557–573. doi: 10.1084/jem.138.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tonegawa S., Hozumi N., Matthyssens G., Schuller R. Somatic changes in the content and context of immunoglobulin genes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):877–889. doi: 10.1101/sqb.1977.041.01.097. [DOI] [PubMed] [Google Scholar]

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