title: FcμR in human B cell subsets in primary selective IgM deficiency, and regulation of FcμR and production of natural IgM antibodies by IGIV.
abstract: IgMFcR (FcμR) are expressed on B cell and B cell subsets. Mice deficient in secreted IgM and FcμR share properties of impaired specific antibody response and autoimmunity with patient with selective IgM deficiency (SIGMD). Intravenous immunoglobulin (IGIV) regulates immune response, including modulation of IgGFc receptors. However, there are no data on the expression of FcμR in patients with SIGMD, and the effects of IGIV on FcμR. In this study, we investigated FcμR expression in naïve marginal zone (MZ), IgM memory, and class-switched memory B cells in patients with selective IgM deficiency and healthy controls. Furthermore, we examined the direct effect of IGIV on FcμR expression and on the upregulation of FcμR by TLR2 agonist (Pam3). Finally, we examined the effect of IVIG on spontaneously produced IgM and natural IgM anti-phosphorylcholine (PC) antibodies by B cells and B1 cells. FcμR expression is significantly decreased in MZ B cells in patients with SIGMD as compared to control. IGIV, at immunomodulatory concentrations, inhibited FcμR upregulation by Pam3 in MZ B cells, and IgM-depleted IGIV inhibited spontaneous secretion of natural IgM anti-PC antibodies and not total IgM by B1 cells. These data suggest that decreased FcμR expression on MZ B cells may play a role in the pathogenesis of SIGMD, and an inhibition of TLR-2-induced upregulation of FcμR by IGIV may be one of the mechanisms of its anti-inflammatory action. IGIV-induced inhibition of natural IgM antibodies may be one of the mechanisms of IGIV-induced immunoregulation.
authors.affiliation: Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, USA. Electronic address: sgupta@uci.edu.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, USA.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, USA.
authors.forename: Sastry
authors.initials: S
authors.lastname: Gollapudi
authors.affiliation: Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kubagawa
mesh_terms: D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D056724:Immunity, Humoral; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000628:therapy; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D051379:Mice; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*
chemical_list: D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; C033027:secretory IgM
keywords: Anti-phosphorylcholine IgM antibodies; FcμR; IGIV; Marginal zone B cells; Natural antibodies; TLR