title: Fyn kinase is required for optimal humoral responses.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Chaimowitz
authors.forename: Yves T
authors.initials: YT
authors.lastname: Falanga
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002452:Cell Count; D055786:Gene Knockout Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D056724:Immunity, Humoral; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D015847:Interleukin-4; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn