Abstract
Mice lacking either CD19 or p110δ have reduced numbers of marginal zone and B1 B cells but normal numbers of naïve B2 cells which occupy the follicles of the lymphoid organs. We show here that mice lacking both CD19 and p110δ have normal B cell development in the bone marrow but have a significant reduction in the number of naïve B2 cells in the bone marrow, spleen and lymph nodes. These p110δ/CD19 double mutant B cells show a survival defect and reduced responsiveness to the pro-survival cytokine BAFF despite normal NFκB2/p100 processing and elevated expression of Bcl-2. Although the combined loss of p110δ and CD19 did not increase switching to Ig-lambda in immature B cells, mature B lymphocytes from the lymph nodes of p110δ/CD19 double mutant mice express highly elevated levels of mRNA encoding RAG-1 and RAG-2, which confirms the existing synergy between CD19 and p110δ-mediated signaling.