Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation

Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen receptor (BCR) signaling. These mice had a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged lyn(-/-) mice developed splenomegaly, produced autoantibodies, and had an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from young lyn(-/-) mice initiated early BCR signaling events, although in a delayed fashion. Unexpectedly, lyn(-/-) B cells exhibited an enhanced MAP kinase activation and an increased proliferative response to BCR engagement. Stimulation of lyn(-/-) B cells with intact and F(ab')(2) anti-IgM revealed defects in at least two mechanisms that negatively regulate BCR signaling, one of which involves Fc gamma RIIb1.