Intraclonal generation of antibody mutants in germinal centres.

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 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.

journal_name

Nature

journal_title

Nature

authors

Jacob J,Kelsoe G,Rajewsky K,Weiss U

doi

10.1038/354389a0

subject

Has Abstract

pub_date

1991-12-05 00:00:00

pages

389-92

issue

6352

eissn

0028-0836

issn

1476-4687

journal_volume

354

pub_type

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