J. Exp. Med., Volume 189, Number 3, February 1, 1999 471-482

Severe Attenuation of the B Cell Immune Response in Msh2-deficient Mice

By Kalpit A. Vora, Kathleen M. Tumas-Brundage, Vicky M. Lentz, Aaron Cranston, Richard Fishel, and Tim Manser

From the Department of Microbiology and Immunology and The Kimmel Cancer Institute,  Jefferson Medical College, Philadelphia, Pennsylvania 19107

Recently, results obtained from mice with targeted inactivations of postreplication DNA mismatch repair (MMR) genes have been interpreted to demonstrate a direct role for MMR in antibody variable (V) gene hypermutation. Here we show that mice that do not express the MMR factor Msh2 have wide-ranging defects in antigen-driven B cell responses. These include lack of progression of the germinal center (GC) reaction associated with increased intra-GC apoptosis, severely diminished antigen-specific immunoglobulin G responses, and near absence of anamnestic responses. Mice heterozygous for the Msh2 deficiency display an "intermediate" phenotype in these regards, suggesting that normal levels of Msh2 expression are critical for the B cell response. Interpretation of the impact of an MMR deficiency on the mechanism of V gene somatic hypermutation could be easily confounded by these perturbations.

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