Syk tyrosine kinase is critical for B cell antibody responses and memory B cell survival Jochen A Ackermann Josquin Nys Edina Schweighoffer Scott McCleary Nicholas Smithers Victor LJ Tybulewicz 10779/crick.12613412.v1 https://crick.figshare.com/articles/journal_contribution/Syk_tyrosine_kinase_is_critical_for_B_cell_antibody_responses_and_memory_B_cell_survival/12613412 Signals from the BCR are required for Ag-specific B cell recruitment into the immune response. Binding of Ag to the BCR induces phosphorylation of immune receptor tyrosine-based activation motifs in the cytoplasmic domains of the CD79a and CD79b signaling subunits, which subsequently bind and activate the Syk protein tyrosine kinase. Earlier work with the DT40 chicken B cell leukemia cell line showed that Syk was required to transduce BCR signals to proximal activation events, suggesting that Syk also plays an important role in the activation and differentiation of primary B cells during an immune response. In this study, we show that Syk-deficient primary mouse B cells have a severe defect in BCR-induced activation, proliferation, and survival. Furthermore, we demonstrate that Syk is required for both T-dependent and T-independent Ab responses, and that this requirement is B cell intrinsic. In the absence of Syk, Ag fails to induce differentiation of naive B cells into germinal center B cells and plasma cells. Finally, we show that the survival of existing memory B cells is dependent on Syk. These experiments demonstrate that Syk plays a critical role in multiple aspects of B cell Ab responses. 2020-07-06 14:08:49 Animals Antibody Formation B-Lymphocytes Cell Differentiation Cell Survival Flow Cytometry Immunologic Memory Intracellular Signaling Peptides and Proteins Lymphocyte Activation Mice Mice, Mutant Strains Protein-Tyrosine Kinases Syk Kinase Tybulewicz U117527252 BRF-ack Immunology 1107 Immunology