Skewed B cell VH family repertoire in Bcl-2-Ig transgenic mice.

The proto-oncogene Bcl-2 is normally expressed in B lineage cells in a stage specific manner and extends cell survival. Deregulated Bcl-2 expression has been shown to cause a major expansion in surface IgM and IgD positive B cells. In this report, the influence of deregulated expression of Bcl-2 on the VH repertoire of B cells was studied. This was accomplished by stimulating B cells from both adult and fetal Bcl-2-Ig transgenic mice and their normal littermates using the polyclonal activator lipopolysaccharide. Activated cells were then analyzed by in situ hybridization using radiolabeled C mu and VH gene probes. The D-proximal VH families 7183 and Q52 were preferentially expressed in the adult transgenic mice compared to their normal littermates. VH 7183 and Q52 were also over-represented in fetal transgenic mice but not to a greater extent than that observed with normal fetuses. These results demonstrate that the overproduction of Bcl-2, which prolongs cell survival independent of affecting proliferation, substantially alters the VH gene repertoire.