Download or read book Cytoskeletal Regulation of B Cell Antigen Receptor Signaling written by Martin Becker and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Signaling through the B cell antigen receptor (BCR) is essential for several processes of B cell biology, such as proliferation, differentiation and homeostasis. Accordingly, the signaling events emanating from the BCR have to be tightly regulated in order to ensure an effective immune response and at the same time avoid pathological conditions like autoimmunity and lymphomagenesis. Mature B cells express two different BCR isotypes, IgM and IgD, which reside in distinct, isotype-specific protein islands on the B cell surface. These structures dependent on the actin cytoskeleton, the disruption of which induces robust BCR signaling, even in the absence of antigen. We here have studied the isotype-specific regulation of the BCR by the cytoskeleton. Using several different genetically engineered mouse models we found that cytoskeleton disruption induced signaling (CDIS) is mediated by the IgD-BCR and the co-receptor CD19. CDIS differs from canonical, antigen-induced BCR signaling in many facets including a lack of BCR proximal tyrosine phosphorylation and induction of a calcium flux originating exclusively from the extracellular space. CDIS can also be enhanced by anti-CD19 stimulation in the absence of a complete IgD- BCR structure as long as the Ig[beta] signaling subunit of the BCR is still expressed on the B cell surface. Together these findings reveal a functional difference between the IgM-BCR and IgD-BCR as well as Ig[alpha] and Ig[beta] in their interactions with CD19 and the actin cytoskeleton. Furthermore, our results provide explanations for the multitude of immunological phenotypes observed in mutants of actin-binding proteins