title: Tolerance induction of IgG+ memory B cells by T cell-independent type II antigens.
abstract: Memory B cells generated during a T cell-dependent immune response rapidly respond to a secondary immunization by producing abundant IgG Abs that bind cognate Ag with high affinity. It is currently unclear whether this heightened recall response by memory B cells is due to augmented IgG-BCR signaling, which has only been demonstrated in the context of naive transgenic B cells. To address this question, we examined whether memory B cells can respond in vivo to Ags that stimulate only through BCR, namely T cell-independent type II (TI-II) Ags. In this study, we show that the TI-II Ag (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll cannot elicit the recall response in mice first immunized with the T cell-dependent Ag NP-chicken γ-globulin. Moreover, the NP-Ficoll challenge in vivo as well as in vitro significantly inhibits a subsequent recall response to NP-chicken γ-globulin in a B cell-intrinsic manner. This NP-Ficoll-mediated tolerance is caused by the preferential elimination of IgG(+) memory B cells binding to NP with high affinity. These data indicate that BCR cross-linking with a TI-II Ag does not activate IgG(+) memory B cells, but rather tolerizes them, identifying a terminal checkpoint of memory B cell differentiation that may prevent autoimmunity.
authors.affiliation: Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Haniuda
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Ohyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D011946:Receptors, Antigen / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D005719:gamma-Globulins / Q000276:immunology
chemical_list: C516150:(4-hydroxy-3-nitrophenyl)acetyl-Ficoll; D000955:Antigens, T-Independent; D007074:Immunoglobulin G; D011946:Receptors, Antigen; D005719:gamma-Globulins; D005362:Ficoll