Fyn kinase is required for optimal humoral responses

• Published in: PloS one 2013-04, Vol.8 (4), p.e60640-e60640
• Main Authors: Chaimowitz, Natalia S, Falanga, Yves T, Ryan, John J, Conrad, Daniel H
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies - metabolism; Antigens; B cells; Biology; Cell Count; Cell survival; Clonal deletion; Cytokines; Defects; Fyn protein; Gene Knockout Techniques; Germinal Center - cytology; Germinal Center - immunology; Germinal centers; Helper cells; Immunity, Humoral; Immunization; Immunoglobulin E; Immunoglobulin G; Immunoglobulins; Immunological memory; Immunology; Interleukin 4; Interleukin-4 - metabolism; Kinases; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Maturation; Memory cells; Mice; Phosphorylation; Plasma cells; Plasma Cells - cytology; Plasma Cells - immunology; Protein-tyrosine kinase; Proto-Oncogene Proteins c-fyn - deficiency; Proto-Oncogene Proteins c-fyn - genetics; Proto-Oncogene Proteins c-fyn - metabolism; Rodents; Signal Transduction - immunology; Signaling; Spleen; Spleen - cytology; T cell receptors; T cells; T-cell receptor; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; Tyrosine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060640

The generation of antigen-specific antibodies and the development of immunological memory require collaboration between B and T cells. T cell-secreted IL-4 is important for B cell survival, isotype switch to IgG1 and IgE, affinity maturation, and the development of germinal centers (GC). Fyn, a member of the Src family tyrosine kinase, is widely expressed in many cell types, including lymphocytes. This kinase is known to interact with both the B cell and T cell receptor (BCR and TCR, respectively). While Fyn deletion does not impair the development of immature T cells and B cells, TCR signaling is altered in mature T cells. The current study demonstrates that Fyn deficient (KO) B cells have impaired IL-4 signaling. Fyn KO mice displayed low basal levels of IgG1, IgE and IgG2c, and delayed antigen-specific IgG1 and IgG2b production, with a dramatic decrease in antigen-specific IgG2c following immunization with a T-dependent antigen. Defects in antibody production correlated with significantly reduced numbers of GC B cells, follicular T helper cells (TFH), and splenic plasma cells (PC). Taken together, our data demonstrate that Fyn kinase is required for optimal humoral responses.