title: gp49B-mediated negative regulation of antibody production by memory and marginal zone B cells.
abstract: The rapid Ab responses observed after primary and secondary immunizations are mainly derived from marginal zone (MZ) and memory B cells, respectively, but it is largely unknown how these responses are negatively regulated. Several inhibitory receptors have been identified and their roles have been studied, but mainly on follicular B cells and much less so on MZ B, and never on memory B cells. gp49B is an Ig superfamily member that contains two ITIMs in its cytoplasmic tail, and it has been shown to negatively regulate mast cell, macrophage, and NK cell responses. In this study, we demonstrate that gp49B is preferentially expressed on memory and MZ B cells. We show that gp49B(-/-) mice produce more IgM after a primary immunization and more IgM and IgG1 after a secondary immunization than gp49B(+/+) mice in T cell-dependent immune responses. Memory and MZ B cells from gp49B(-/-) mice also produce more Abs upon in vitro stimulation with CD40 than those from gp49B(+/+) mice. The in vitro IgM production by MZ B cells from gp49B(+/+), but not gp49B(-/-), mice is suppressed by interaction with a putative gp49B ligand, the integrin αvβ3 heterodimer. In addition, gp49B(-/-) mice exhibited exaggerated IgE production in the memory recall response. These results suggest that plasma cell development from memory and MZ B cells, as well as subsequent Ab production, are suppressed via gp49B. In memory B cells, this suppression also prevents excessive IgE production, thus curtailing allergic diseases.
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; and.
authors.forename: Saori
authors.initials: S
authors.lastname: Fukao
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; and.
authors.forename: Kei
authors.initials: K
authors.lastname: Haniuda
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; and.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; and kitamura@rs.noda.tus.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D041702:BALB 3T3 Cells; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002645:Chickens; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005719:gamma-Globulins / Q000276:immunology
chemical_list: C516150:(4-hydroxy-3-nitrophenyl)acetyl-Ficoll; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D039302:Integrin alphaVbeta3; C489448:Lilrb4 protein, mouse; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D005719:gamma-Globulins; D005362:Ficoll; D007073:Immunoglobulin E