Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65

During signal transduction through the B cell antigen receptor (BCR), sever al signaling elements are brought together by the adaptor protein SLP-65. W e have investigated the role of SLP-65 in B cell maturation and function in mice deficient for SLP-65. While the mice are viable, B cell development i s affected at several stages. SLP-65-deficient mice show increased proporti ons of pre-B cells in the bone marrow and immature B cells in peripheral ly mphoid organs. B1 B cells are lacking. The mice show tower IgM and IgG3 ser um titers and poor IgM but normal IgG immune responses. Mutant B cells show reduced Ca2+ mobilization and reduced proliferative responses to B cell mi togens. We conclude that white playing an important role, SLP-65 is not alw ays required for signaling from the BCR.