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 h igher than normal turnover rate. Aged lyn(-/-) mice developed splenome galy, produced autoantibodies, and had an expanded population of B lym phoblasts of the B1 lineage. Splenic B cells from young lyn(-/-) mice initiated early BCR signaling events, although in a delayed fashion. U nexpectedly, lyn(-/-) B cells exhibited an enhanced MAP kinase activat ion and an increased proliferative response to BCR engagement. Stimula tion of lyn(-/-) B cells with intact and F(ab')(2) anti-IgM revealed d efects in at least two mechanisms that negatively regulate BCR signali ng, one of which involves Fc gamma RIIb1.