title: B Cell-intrinsic TLR7 signaling is required for optimal B cell responses during chronic viral infection.
abstract: The importance for activation of innate immunity by pattern recognition receptors in forming an effective adaptive immune response is well known. TLRs were demonstrated to be critical for Ab responses to a variety of immunizations. In particular, recent evidence suggests that B cell-intrinsic TLR signaling is required for optimal responses to virus-like Ags, but the mechanisms by which TLR signaling impacts Ab responses during infection in vivo is unclear. In the current study, we demonstrate that deficiency of TLR7 in B cells alone is sufficient to significantly impact Ab responses in mice during chronic viral infection. This effect was independent of T follicular helper cells and resulted in a loss of plasma cells generated later, but not early, in the response. The defect in plasma cell formation appeared to be secondary to a qualitative effect of TLR signaling on the germinal center (GC) B cell response. GC B cells in TLR7-deficient mice proliferated to a lesser extent and had a greater proportion of cells with phenotypic characteristics of light zone, relative to dark zone, GC B cells. These results suggest that B cell-intrinsic TLR signaling in vivo likely affects plasma cell output by altered selection of Ag-specific B cells in the GC.
authors.affiliation: Division of Rheumatology, Department of Medicine and Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Clingan
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Matloubian
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D007074:Immunoglobulin G / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D051192:Receptors, Pattern Recognition; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7