Expression of the B cell repertoire in lpr mice; abnormal expansion of a few VHJ558 germ-line genes.

Abstract

Analysis of the VH gene repertoire of the J558 family was done in lipopolysaccharide (LPS)-stimulated resting cells and in vivo activated cells derived from C57Bl/6-lpr mice (IghCb). Using a restriction fragment length polymorphism (RFLP) based on digestion with the restriction enzyme Pstl, the expression of the subfamilies of the J558 family of VH genes could be determined. The J558 subfamily repertoire of resting B cells of the lpr mice was similar to that of the normal mice, while the J558 repertoire of the in vivo-activated cells was altered: analysis and sequencing of the IgM-expressed J558 repertoire of a sick female mouse showed that 50% of the J558 genes were represented by a single VH gene rearrangement, showing that its expansion was monoclonal. Furthermore, this same rearrangement made up to 90% of the J558 repertoire in the IgG2a+ population, showing that it had been preferentially selected, expanded and switched. However, compared with its IgM counterpart, it showed no evidence of somatic hypermutation.