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Intraclonal generation of antibody mutants in germinal centres

Nature volume 354, pages 389–392 (1991)Cite this article

Abstract

THE generation and selection of somatic antibody mutants are key elements of acquired immunity, essential for the affinity maturation of antibody responses dependent on T cells. The mutants are generated through a mechanism that introduces point mutations at high rate into rearranged variable (V) region genes in the course of cell proliferation1,2. Their appearance coincides with the generation of germinal centres, which are characterized by oligoclonal B-cell proliferation3,4 and have been suggested to be the microen-vironment in which antibody mutants are generated5,6. We report here direct evidence for this hypothesis. Rearranged V-region genes were amplified from the genomic DNA of cells picked from individual germinal centres. The sequence analysis of these genes revealed that most represent cells of distinct B-cell clones which expanded locally, generating somatic antibody mutants at high rate. By contrast, antigen-induced proliferation of B cells at another site, periarteriolar lymphocyte sheath-associated foci, was not associated with somatic hypermutation.

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Author notes

  1. Ursula Weiss: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA

    Joshy Jacob & Garnett Kelsoe

  2. Institute for Genetics, University of Cologne, Weyertal 121, D-5000, Cologne, 41, Germany

    Klaus Rajewsky & Ursula Weiss

Authors
  1. Joshy Jacob
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  2. Garnett Kelsoe
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  3. Klaus Rajewsky
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  4. Ursula Weiss
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Jacob, J., Kelsoe, G., Rajewsky, K. et al. Intraclonal generation of antibody mutants in germinal centres. Nature 354, 389–392 (1991). https://doi.org/10.1038/354389a0

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