title: IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF.
abstract: Memory B cell responses are vital for protection against infections but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high-affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG-immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent Ag leads to IC-FcγR interactions that induce dendritic cells to secrete BAFF, which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary Ab responses. BAFF also contributed to the maintenance and/or expansion of the follicular helper T cell population, although it was dispensable for their formation. Thus, early Ab responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: SunAh
authors.identifier: http://orcid.org/0000-0002-6327-184X
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Keener
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Shannon Z
authors.initials: SZ
authors.lastname: Jones
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Benschop
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710;
authors.forename: Alfredo
authors.initials: A
authors.lastname: Caro-Maldonado
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710;
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Rathmell
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Clarke
authors.affiliation: Neuroscience Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; barb_vilen@med.unc.edu.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Vilen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D053264:B-Cell Activating Factor; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D051560:Proto-Oncogene Proteins c-bcl-6; D017452:Receptors, IgG; C505720:Tnfsf13b protein, mouse