The B cell receptor (BCR) serves as both signal-transducer and antigen-transporter. Binding of antigens to the BCR induces signaling cascades and antigen-processing and presentation, two essential cellular events for B cell activation. BCR-initiated signaling increases BCR-mediated antigen-processing efficiency by increasing the rate and specificity of antigen transport. Previous studies showed a critical role for the actin cytoskeleton in these two processes. Here I found that actin-binding protein 1 (Abp1/HIP-55/SH3P7) functioned as an actin-binding adaptor protein, coupling BCR signaling and antigen-processing pathways with the actin cytoskeleton. Gene knockout of Abp1 and over-expression of the SH3 domain of Abp1 inhibited BCR-mediated antigen internalization, consequently reducing the rate of antigen transport to processing compartments and the efficiency of BCR-mediated antigen-processing and presentation. BCR activation induced tyrosine phosphorylation of Abp1 and translocation of both Abp1 and dynamin 2 from the cytoplasm to the plasma membrane, where they colocalized with the BCR and cortical F-actin. The inhibitory effect of a dynamin PRD deletion mutant on the recruitment of Abp1 to the plasma membrane and the

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Oligomerization of the B-cell receptor (BCR) by antigen leads to both signal transduction and antigen internalization for processing and presentation. Previous studies indicate that these processes intersect at the actin cytoskeleton to coordinate the two cellular processes for the optimal activation of B-cells. The exact mechanism by which signals are transduced via the actin cytoskeleton into the efficient internalization and transport of BCR-antigen complexes is not well delineated. In this thesis, I demonstrate that Bruton’s tyrosine kinase (Btk), a Tec kinase in the early signaling pathway of the BCR, is able to transduce signals from the BCR to actin regulatory proteins such as WASP and N-WASP. Upon BCR activation, Btk modulates actin dynamics by increasing the levels of phosphorylated, active WASP and N-WASP in B-cells. Btk regulates the activity of WASP and N-WASP by increasing the levels of PtdIns-4,5-P2 and phosphorylated Vav, both of which are required for WASP and N-WASP activation. Inhibition of Btk activity by a point mutation or a specific inhibitor prevents BCR-induced increases in PtdIns-4,5-P2 as well as in phosphorylated WASP, N-WASP and Vav. Furthermore, Btk deficiency or