The Journal of Immunology, Vol 159, Issue 7 3347-3353, Copyright © 1997 by American Association of Immunologists

ARTICLES

In vitro triggering of somatic mutation in human naive B cells

D Razanajaona, S Denepoux, D Blanchard, O de Bouteiller, YJ Liu, J Banchereau and S Lebecque
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.

During T cell-dependent immune response, germinal center B cells accumulate somatic mutations in their Ig V(D)J genes and give rise to affinity-selected B cells. We tested several culture conditions for triggering somatic mutation in human tonsillar naive slgD+CD23+ cells after cross-linking their membrane Igs. CD40 activation, in the presence of exogenous cytokines (IL-2, IL-4, and IL-10), induced proliferation and isotype switch without somatic mutation. In contrast, after coculture with anti-CD3-activated cloned T cells, somatic mutation accumulated in a fraction of naive B cells. Mutations included shared as well as independent events in clonally related sequences, allowing reconstitution of genealogic trees generated in vitro. Naive tonsillar B cells sorted for slgD expression can be induced to mutate their Ig V(H) gene upon coculture with activated T cells, thereby providing a model to study somatic hypermutation in vitro.

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