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

Protein kinase Cβ (PKCβ) expressed in mammalian cells as two splice variants, PKCβI and PKCβII, functions in the B cell receptor (BCR) signaling pathway and contributes to B cell development. We investigated the relative role of PKCβII in B cells by generating transgenic mice where expression of the transgene is directed to these cells using the Eµ promoter (Eµ-PKCβIItg). Our findings demonstrate that homozygous Eµ-PKCβIItg mice displayed a shift from IgD⁺IgM^dim toward IgD^dimIgM⁺ 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^negCD21⁺CD24⁺), increased populations of B-1 cells (B220⁺IgD^dimIgM⁺CD43⁺CD24⁺CD5⁺), and higher numbers of immature B cells (IgD^dimIgM^dimCD21^neg) at the expense of mature B cells (IgD⁺IgM⁺CD21⁺). Therefore, the overexpression of PKCβII, 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.