Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

Rika Ouchida, Hiromi Mori, Kouji Hase, Hiroyuki Takatsu, Tomohiro Kurosaki, Takeshi Tokuhisa, Hiroshi Ohno, Ji Yang Wang

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

IgM antibodies have been known for decades to enhance humoral immune responses in an antigen-specific fashion. This enhancement has been thought to be dependent on complement activation by IgM-antigen complexes; however, recent genetic studies render this mechanism unlikely. Here, we describe a likely alternative explanation; mice lacking the recently identified Fc receptor for IgM (FcμR) on B cells produced significantly less antibody to protein antigen during both primary and memory responses. This immune deficiency was accompanied by impaired germinal center formation and decreased plasma and memory B-cell generation. FcμR did not affect steady-state B-cell survival but specifically enhanced the survival and proliferation induced by B-cell receptor cross-linking. Moreover, FcμR-deficient mice produced far more autoantibodies than control mice as they aged, suggesting that FcμR is also required for maintaining tolerance to self-antigens. Our results thus define a unique pathway mediated by the FcμR for regulating immunity and tolerance and suggest that IgM antibodies promote humoral immune responses to foreign antigen yet suppress autoantibody production through at least two pathways: complement activation and FcμR.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number40
DOIs
Publication statusPublished - 2012 Oct 2
Externally publishedYes

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Humoral Immunity
Immunoglobulin M
Cell Survival
Homeostasis
B-Lymphocytes
Complement Activation
Antigens
Autoantibodies
Antibodies
Complement Receptors
Germinal Center
Fc Receptors
Histocompatibility Antigens Class II
Autoantigens
Immunity
immunoglobulin M receptor
Proteins

Keywords

  • Autoimmune disease
  • B-cell activation
  • Complement receptor

ASJC Scopus subject areas

  • General

Cite this

Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. / Ouchida, Rika; Mori, Hiromi; Hase, Kouji; Takatsu, Hiroyuki; Kurosaki, Tomohiro; Tokuhisa, Takeshi; Ohno, Hiroshi; Wang, Ji Yang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 40, 02.10.2012.

Research output: Contribution to journalArticle

Ouchida, Rika ; Mori, Hiromi ; Hase, Kouji ; Takatsu, Hiroyuki ; Kurosaki, Tomohiro ; Tokuhisa, Takeshi ; Ohno, Hiroshi ; Wang, Ji Yang. / Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 40.
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AU - Kurosaki, Tomohiro

AU - Tokuhisa, Takeshi

AU - Ohno, Hiroshi

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