A novel transgenic mouse strain expressing PKCβII demonstrates expansion of B1 and marginal zone B cell populations

Protein kinase C beta (PKC beta) expressed in mammalian cells as two splice variants, PKC beta I and PKC beta II, functions in the B cell receptor (BCR) signaling pathway and contributes to B cell development. We investigated the relative role of PKC beta II in B cells by generating transgenic mice where expression of the transgene is directed to these cells using the E mu promoter (E mu -PKC beta IItg). Our findings demonstrate that homozygous E mu -PKC beta IItg mice displayed a shift from IgD(+)IgM(dim) toward IgD(dim)IgM(+) B cell populations in spleen, peritoneum and peripheral blood. Closer examination of these tissues revealed respective expansion of marginal zone (MZ)-like B cells (IgD(+)IgM(+)CD43(neg)CD21(+)CD24(+)), increased populations of B-1 cells (B220(+)IgD(dim)IgM(+)CD43(+)CD24(+)CD5(+)), and higher numbers of immature B cells (IgD(dim)IgM(dim)CD21(neg)) at the expense of mature B cells (IgD(+)IgM(+)CD21(+)). Therefore, the overexpression of PKC beta II, which is a phenotypic feature of chronic lymphocytic leukaemia cells, can skew B cell development in mice, most likely as a result of a regulatory influence on BCR signaling.