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. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776

The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice

PMCID: PMC2184201  PMID: 416167

Abstract

The primary immune response of BALB/c mice to influenza (PR8) hemagglutinin (HA), a complex protein antigen, has been examined by the splenic focus assay, and the resulting monoclonal anti-HA antibodies have been characterized by their reactivity with heterologous viruses. The analysis of the primary B-cell response to HA revealed marked differences from responses previously defined for haptenic determinants. There were following differences: (a) the frequency of HA- specific B cells in both conventional and germ-free BALB/c mice was 1 in 1.0-1.5 X 10(5) splenic B cells, which is substantially lower than the frequency of B cells responsive to various simple haptenic determinants; (b) monoclonal anti-HA antibodies were predominantly of the IgA or IgM isotypes instead of IgG, which dominates antihapten responses; and (c) after immunization, the frequency of anti-HA- specific B cells increases by 10- to 50-fold, which is much greater increase than that observed after immunization with haptenic determinants. Fine specificity analysis of primary monoclonal HA- specific antibodies revealed extensive diversity and a considerable overlap with the specificities obtained from immune mice. Given the low overall frequency of HA-specific B cells, it could be calculated that the representation of most HA-specific clonotypes within the B-cell repertoire could not exceed 1 in 10(7) B cells. These findings indicate that the primary B-cell clonotype repertoire is extremely diverse and largely antigen independent in its generation.

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Selected References

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  1. Berek C., Taylor B. A., Eichmann K. Genetics of the idotype of BALB/c myeloma S117: multiple chromosomal loci for Vh genes encoding specificity for group A streptococcal carbohydrate. J Exp Med. 1976 Nov 2;144(5):1164–1174. doi: 10.1084/jem.144.5.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Cancro M. P., Sigal N. H., Klinman N. R. Differential expression of an equivalent clonotype among BALB/c and C57BL/6 mice. J Exp Med. 1978 Jan 1;147(1):1–12. doi: 10.1084/jem.147.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Claflin J. L., Lieberman R., Davie J. M. Clonal nature of the immune response to phosphorylcholine. II. Idiotypic specificity and binding characteristics of anti-phosphorylcholine antibodies. J Immunol. 1974 May;112(5):1747–1756. [PubMed] [Google Scholar]
  5. Cosenza H., Köhler H. Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody. Science. 1972 Jun 2;176(4038):1027–1029. doi: 10.1126/science.176.4038.1027. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fazekas de St Groth, Webster R. G. Disquisitions of Original Antigenic Sin. I. Evidence in man. J Exp Med. 1966 Sep 1;124(3):331–345. doi: 10.1084/jem.124.3.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Gerhard W., Braciale T. J., Klinman N. R. The analysis of the monoclonal immune response to influenza virus. I. Production of monoclonal anti-viral antibodies in vitro. Eur J Immunol. 1975 Oct;5(10):720–725. doi: 10.1002/eji.1830051013. [DOI] [PubMed] [Google Scholar]
  10. Gerhard W. The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin. J Exp Med. 1976 Oct 1;144(4):985–995. doi: 10.1084/jem.144.4.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Imanishi T., Makela O. Inheritance of antibody specificity. II. Anti-(4-hydroxy-5-bromo-3-nitrophenyl) acetyl in the mouse. J Exp Med. 1975 Apr 1;141(4):840–854. [PMC free article] [PubMed] [Google Scholar]
  12. Klinman N. R., Aschinazi G. The stimulation of splenic foci in vitro. J Immunol. 1971 May;106(5):1338–1344. [PubMed] [Google Scholar]
  13. 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]
  14. Klinman N. R., Press J. L., Segal G. P. Overlap stimulation of primary and secondary B cells by cross-reacting determinants. J Exp Med. 1973 Nov 1;138(5):1276–1281. doi: 10.1084/jem.138.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Köhler G. Frequency of precursor cells against the enzyme beta-galactosidase: an estimate of the BALB/c strain antibody repertoire. Eur J Immunol. 1976 May;6(5):340–347. doi: 10.1002/eji.1830060507. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Mäkelä O., Imanishi T. Expression of an immunoglobulin VH gene in natural anti-hapten antibodies. Eur J Immunol. 1975 Mar;5(3):202–205. doi: 10.1002/eji.1830050310. [DOI] [PubMed] [Google Scholar]
  19. Mäkelä O., Julin M., Becker M. Inheritance of antibody specificity. III. A new VH gene controls fine specificity of anti-p-azobenzenearsonate coupled to the carbon atom 5 of hydroxyphenylacetic acid in the mouse. J Exp Med. 1976 Feb 1;143(2):316–328. doi: 10.1084/jem.143.2.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pawlak L. L., Nisonoff A. Distribution of a cross-reactive idiotypic specificity in inbred strains of mice. J Exp Med. 1973 Apr 1;137(4):855–869. doi: 10.1084/jem.137.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pierce S. K., Klinman N. R. Antibody-specific immunoregulation. J Exp Med. 1977 Aug 1;146(2):509–519. doi: 10.1084/jem.146.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Press J. L., Klinman N. R. Monoclonal production of both IgM and IgG1 antihapten antibody. J Exp Med. 1973 Jul 1;138(1):300–305. doi: 10.1084/jem.138.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Sigal N. H. The frequency of para-azophenylarsonate and dimethylaminonapthalene-sulfonyl-specific B cells in neonatal and adult BALB/c mice. J Immunol. 1977 Sep;119(3):1129–1133. [PubMed] [Google Scholar]
  26. 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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