title: B7-1/2 (CD80/CD86) direct signaling to B cells enhances IgG secretion.
abstract: B cell responses are regulated by Ag recognition, costimulatory signals provided by interaction with helper T cells, and by innate signals. We recently provided evidence for a link between the effects of innate and costimulatory signals on B cells during influenza virus infection, by demonstrating that most B cells in the regional lymph nodes of the respiratory tract enhance surface expression of the costimulator B7-2 (CD86) within 24-48 h following infection via a type I IFNR-dependent mechanisms, a finding we are confirming here. While the role of B7-1/2 for helper T cell activation is well documented, its role in direct B cell regulation is poorly understood. Here, our in vivo studies with mixed bone marrow irradiation chimeric mice, lacking B7-1/2 only on B cells, demonstrated that B7-1/2 expression is crucial for induction of maximal local, but to a lesser extent systemic, IgG Ab responses following influenza virus infection. In contrast to mice that completely lack B7-1/2 expression, loss of B7-1/2 on B cells alone did not significantly affect germinal center formation or the extent of CD4(+) T cell activation and IFN-gamma secretion. Instead, our in vitro studies identify a dramatic effect of B7-2 engagement on IgG, but not IgM secretion by already class-switched B cells. Concomitantly, B7-2 engagement induced expression of X-box binding protein 1 (XBP-1) and spliced XBP1, evidence for increased protein synthesis by these cells. Taken together, these results identify direct signaling through B7-1/2 as a potent regulator of IgG secretion by previously activated B cells.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Friederike C
authors.initials: FC
authors.lastname: Rau
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Dieter
authors.forename: Zhang
authors.initials: Z
authors.lastname: Luo
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Priest
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D051940:B7-2 Antigen / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M