title: Enhanced humoral immune responses against T-independent antigens in Fc alpha/muR-deficient mice.
abstract: IgM is an antibody class common to all vertebrates that plays a primary role in host defenses against infection. Binding of IgM with an antigen initiates the complement cascade, accelerating cellular and humoral immune responses. However, the functional role of the Fc receptor for IgM in such immune responses remains obscure. Here we show that mice deficient in Fc alpha/muR, an Fc receptor for IgM expressed on B cells and follicular dendritic cells (FDCs), have enhanced germinal center formation and affinity maturation and memory induction of IgG3(+) B cells after immunization with T-independent (TI) antigens. Moreover, Fc alpha/muR-deficient mice show prolonged antigen retention by marginal zone B (MZB) cells and FDCs. In vitro studies demonstrate that interaction of the IgM immune complex with Fc alpha/muR partly suppress TI antigen retention by MZB cells. We further show that downregulation of complement receptor (CR)1 and CR2 or complement deprivation by in vivo injection with anti-CR1/2 antibody or cobra venom factor attenuates antigen retention by MZB cells and germinal center formation after immunization with TI antigens in Fc alpha/muR(-/-) mice. Taken together, these results suggest that Fc alpha/muR negatively regulates TI antigen retention by MZB cells and FDCs, leading to suppression of humoral immune responses against T-independent antigens.
authors: Department of Immunology and Anatomy, Graduate School of Comprehensive Human Sciences, and Center for TARA, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors: Shin-ichiro
authors: S
authors: Honda
authors: Naoki
authors: N
authors: Kurita
authors: Akitomo
authors: A
authors: Miyamoto
authors: Yukiko
authors: Y
authors: Cho
authors: Kenta
authors: K
authors: Usui
authors: Kie
authors: K
authors: Takeshita
authors: Satoru
authors: S
authors: Takahashi
authors: Teruhito
authors: T
authors: Yasui
authors: Hitoshi
authors: H
authors: Kikutani
authors: Taroh
authors: T
authors: Kinoshita
authors: Teizo
authors: T
authors: Fujita
authors: Satoko
authors: S
authors: Tahara-Hanaoka
authors: Kazuko
authors: K
authors: Shibuya
authors: Akira
authors: A
authors: Shibuya
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D011961:Receptors, Fc / Q000172:deficiency* / Q000276:immunology*
chemical_list: D000955:Antigens, T-Independent; C526791:Fcalpha-mu protein, mouse; D007074:Immunoglobulin G; D011961:Receptors, Fc; D003165:Complement System Proteins