ANALYSIS OF SOMATIC HYPERMUTATION IN MOUSE PEYER PATCHES USING IMMUNOGLOBULIN-KAPPA LIGHT-CHAIN TRANSGENES

We have exploited mice transgenic for an immunoglobulin kappa light ch ain in order to show thal immunoglobulin genes in the B cells of Peyer 's patches in unimmunized mice carry a high level of somatic mutations . Most of the mutations are found in the subpopulation of B cells whic h, based on peanut agglutinin binding, derive from the germinal center s. The number of mutations per clone and their distribution along the variable gene segment (indicative of untemplated point mutations) are very similar to those found in antigen-specific splenic B cells of nor mal mice after secondary immunization. The mutations accumulate mainly in complementarity-determining region 1, in particular in some specif ic codons (Ser-26, Ser-31, and Ser-77) which have been previously reco gnized as intrinsic hypermutational hotspots. These results suggest th at, as in the spleen, somatic mutation occurs in B cells which have mi grated to the germinal centers, probably as a consequence of stimulati on by antigens present in the gut environment. Transgenic animals are increasingly being used to define the signals involved in hypermutatio n. However, their subsequent study is very time-consuming because it i s based on immunization and analysis of hybridomas or antigen-selected cells. We propose that the use of Peyer's patches of unimmunized adul t mice offers a reliable and simple approach to analyze hypermutation of transgenes.