Recently, results obtained from mice with targeted inactivations of postrep
lication DNA mismatch repair (MMR) genes have been interpreted to demonstra
te 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 progress
ion 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 g
ene somatic hypermutation could be easily confounded by these perturbations
.