Loss of λ2315 transgene copy numbers influences the development of B1 cells

Abstract

Transgenic L2 mice contain high numbers of the λ2315 immunoglobulin L chain gene in their germ line. They are characterized by an almost complete block in B2 cell development and dominance of B1 cells in their periphery. This was attributed to high transgene expression. Here, we describe a variant of such mice (L2V), which has lost half of the transgene copies. This results in decreased transgene expression. Consequently, such mice display less severe isotype exclusion and an increase in B cells expressing endogenous κ light chains. In addition, the B2 cell compartment is enlarged. Nevertheless, L2V mice exhibit phosphatidylcholine (PtC) binding B cells expressing λ L chains as well as an unaltered number of B1a cells expressing the dominating specificity usually encountered in L2 mice. Since in L2V mice transgene integration and regulation is identical to L2 mice, the correlation of decreased transgene expression and increased presence of B2 cells strongly suggests that high transgene expression is decisive for development of B1 cells in L2 mice.