The role of Actin Binding Protein One (Abp1) in B cell development, activation, and B cell tolerance. (132.23)

Abstract

Abstract The B cell receptor (BCR) serves as both signal-transducer and antigen-transporter. Optimal activation of B cells depends on coordinated BCR signaling, antigen processing, and actin cytoskeleton rearrangement events. Actin-binding protein 1 (Abp1/HIP-55/SH3P7) is a unique adaptor protein that has been shown to directly interact with components of signal transduction, endocytosis, and actin cytoskeleton apparatuses through its proline-rich, SH3, and actin binding domains. This suggests a role for Abp1 in mediating cross-talk among the three cell apparatuses during BCR activation. Here we study the role of Abp1 in B cell development, activation, and B cell tolerance. We discovered major defects in B cell development in Abp1 knockout mice, exhibited as reduced numbers of pre- and immature B cells in the bone marrow, and transitional B cells in the spleen. Furthermore, Abp1 knockout mice exhibit splenomegaly and have increased levels of anti-nuclear antibodies. At the cellular level, Abp1 is recruited to BCR surface signalosomes in response to antigenic stimulation. In Abp1 knockout mice, BCR-induced protein tyrosine phosphorylation of splenic B cells is elevated and phosphorylation of the MAP kinase JNK reduced compared to wild type B cells. These results suggest that Abp1 can regulate B cell development, B cell activation, and B cell tolerance via modulation of BCR signaling. This work supported by a NIH grant (AI059617) for W.S.