title: Syk tyrosine kinase is critical for B cell antibody responses and memory B cell survival.
abstract: 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.
authors: Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom; and.
authors: Jochen A
authors: JA
authors: Ackermann
authors: Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom; and.
authors: Josquin
authors: J
authors: Nys
authors: Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom; and.
authors: Edina
authors: E
authors: Schweighoffer
authors: Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom.
authors: Scott
authors: S
authors: McCleary
authors: Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom.
authors: Nicholas
authors: N
authors: Smithers
authors: Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom; and Victor.T@crick.ac.uk.
authors: Victor L J
authors: http://orcid.org/0000-0003-2439-0798
authors: VL
authors: Tybulewicz
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse