The Influence of Somatic Mutation on Clonal Expansion

  • M. J. Shlomchik
  • S. Litwin
  • M. Weigert


The key feature of the process of somatic diversification is that mutations accumulate sequentially during clonal expansion. This was first recognized from the hierarchy of shared mutations in antibodies from clonally related lymphocytes (McKean et al. 1984) and supported by the finding that the frequency of mutations increases during the immune response to antigen (Berek et al. 1985). Although the mechanism of mutation is still a mystery, one consequence is to introduce discrete point mutations into expressed V genes. This is readily observed among antibodies at initial stages of diversification when expressed V genes can differ from their germline counterparts by single base changes (Weigert et al. 1970) and among clonally related antibodies where siblings differ from each other by single base changes (for example, Radie et al. 1989). Thus the high frequency of mutations in Y genes of antibodies from the secondary response to antigen is likely due to the sequential accumulation of point mutations.


Somatic Mutation Negative Selection Clonal Expansion Burst Size Single Base Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berek C, Griffiths, GM, Milstein C (1985) Molecular events during maturation of the immune response to oxazolone. Nature 316:412–418PubMedCrossRefGoogle Scholar
  2. Blier PR, Both well A (1987) A limited number of B cell lineages generates the heterogeneity of a secondary immune response. J Immunol 139:3996–4006PubMedGoogle Scholar
  3. Caton A, Brownlee G, Staudt L, Gerhard W (1986) Structural and functional implications of a restricted antibody response to a defined antigenic region on the influenza virus hemagglutinin. EMBO J 5:1577–1591PubMedCentralPubMedGoogle Scholar
  4. Clarke S, Hüppi K, Ruezinsky D, Staudt L, Gerhard W, Weigert MG (1985) Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J Exp Med 161:687–704PubMedCrossRefGoogle Scholar
  5. Cumano A, Rajewsky K (1986) Clonal recruitment and somatic mutation in the generation of immunological memory to the hapten NP. EMBO J 5:2459–1468PubMedCentralPubMedGoogle Scholar
  6. Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185:862–864PubMedCrossRefGoogle Scholar
  7. Jukes TH, King IL (1979) Evolutionary nucleotide replacements in DNA. Nature 281:605–606PubMedCrossRefGoogle Scholar
  8. Kabat EA, Wu TT, Bilofsky H, Reid-Miller M, Perry H (1983) U.S. Government Printing Office, Bethesda, MDGoogle Scholar
  9. Levy NS, Malipiero UV, Lebeque SG, Gearhart PJ (1989) Early onset of somatic mutation in immunoglobulin VHgenes during the primary immune response. J Exp Med 169:2007–2019PubMedCrossRefGoogle Scholar
  10. McKean D, Hüppi K, Bell M, Staudt L, Gerhard W, Weigert M (1984) Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc Natl Acad Sci USA 81:3180–3184CrossRefGoogle Scholar
  11. Newman TG, Odell PL (1971) Griffin’s Statistical Monographs and Courses, No. 29. Hafner Publishing Coxx.Google Scholar
  12. Padlan EA (1977) Structural implications of sequence variability in immunoglobulins. Proc Natl Acad Sci USA 74:2551–2555PubMedCentralPubMedCrossRefGoogle Scholar
  13. Potter M, Newell JB, Rudikoff S, Haber E (1982) Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: Impact of 14 new sequences from IgG myeloma proteins. Mol Immunol 19:1619–1630PubMedCrossRefGoogle Scholar
  14. Radic MZ, Mascelli MA, Erikson J, Shan H, Shlomchik MJ, Weigert M (in press) Cold Spring Harbor Symp Quant BiolGoogle Scholar
  15. Sharon J (1988) The invariant tryptophan in an H chain V region is not essential to antibody binding. J Immunol 140:2666–2669Google Scholar
  16. Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG (1987a) The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811PubMedCrossRefGoogle Scholar
  17. Shlomchik MJ, Aucoin AH, Pisetsky DS, Weigert MG (1987b) Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci USA 84:9150–9154PubMedCentralPubMedCrossRefGoogle Scholar
  18. Siekevitz M, Kocks C, Rajewsky K, Dildrop R (1987) Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses. Cell 48:757–770PubMedCrossRefGoogle Scholar
  19. Weigert M (1986) The influence of somatic mutation on the immune response. In: Cinader B, Miller RG (eds) Progress in Immunology VI. Academic Press, New York, p 138CrossRefGoogle Scholar
  20. Weigert MG, Cesari IM, Yonkovich SJ, Cohn M (1970) Variability in the lambda light chain sequences of mouse antibody. Nature 228:1045–1047PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. J. Shlomchik
  • S. Litwin
  • M. Weigert

There are no affiliations available

Personalised recommendations