Intraclonal generation of antibody mutants in germinal centres.

Journal Article

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 proliferation. Their appearance coincides with the generation of germinal centres, which are characterized by oligoclonal B-cell proliferation and have been suggested to be the microenvironment in which antibody mutants are generated. 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.

Full Text

Duke Authors

Cited Authors

  • Jacob, J; Kelsoe, G; Rajewsky, K; Weiss, U

Published Date

  • December 5, 1991

Published In

Volume / Issue

  • 354 / 6352

Start / End Page

  • 389 - 392

PubMed ID

  • 1956400

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/354389a0

Language

  • eng

Conference Location

  • England