title: Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice.
abstract: The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas (lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(-) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcμR(-) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcμR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcμR(-) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcμR(-) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Fas (lpr/lpr) mice.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Honjo
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kubagawa
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: R Pat
authors.initials: RP
authors.lastname: Bucy
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA hiromikubagawa@uab.edu.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kubagawa
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018655:Lymphocyte Count; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D009393:Nephritis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011961:Receptors, Fc / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology
chemical_list: D001323:Autoantibodies; D011961:Receptors, Fc; D017411:Ribonucleoproteins, Small Nuclear; C035311:immunoglobulin M receptor
keywords: FcμR; IgM; Mott cells; auto-antibody; marginal zone B cells