SIgM-fcmr interactions regulate early b cell activation and plasma cell development after influenza virus infection

Trang T.T. Nguyen, Beth A. Graf, Troy D. Randall, Nicole Baumgarth

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Abstract

Previous studies with mice lacking secreted IgM(sIgM) due to a deletion of the ms splice region (ms2/2) had shown sIgM involvement in normal B cell development and in support of maximal Ag-specific IgG responses. Because of the changes to B cell development, it remains unclear to which extent and how sIgM directly affects B cell responses. In this study, we aimed to explore the underlying mechanisms of sIgM-mediated IgG response regulation during influenza virus infection. Generating mice with normally developed ms-deficient B cells, we demonstrate that sIgM supports IgG responses by enhancing early Ag-specific B cell expansion, not by altering B cell development. Lack of FcmR expression on B cells, but not lack of Fca/mR expression or complement activation, reduced antiviral IgG responses to the same extent as observed in ms2/2 mice. B cell-specific Fcmr2/2 mice lacked robust clonal expansion of influenza hemagglutinin-specific B cells early after infection and developed fewer spleen and bone marrow IgG plasma cells and memory B cells, compared with controls. However, germinal center responses appeared unaffected. Provision of sIgM rescued plasma cell development from ms2/2 but not Fcmr2/2 B cells, as demonstrated with mixed bone marrow chimeric mice. Taken together, the data suggest that sIgM interacts with FcmR on B cells to support early B cell activation and the development of long-lived humoral immunity.

Original languageEnglish (US)
Pages (from-to)1635-1646
Number of pages12
JournalJournal of Immunology
Volume199
Issue number5
DOIs
StatePublished - Sep 1 2017

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Virus Diseases
Plasma Cells
Orthomyxoviridae
B-Lymphocytes
Immunoglobulin M
Immunoglobulin G
Bone Marrow
Germinal Center
Complement Activation
Hemagglutinins
Humoral Immunity
Human Influenza
Antiviral Agents
Spleen

ASJC Scopus subject areas

  • Immunology

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SIgM-fcmr interactions regulate early b cell activation and plasma cell development after influenza virus infection. / Nguyen, Trang T.T.; Graf, Beth A.; Randall, Troy D.; Baumgarth, Nicole.

In: Journal of Immunology, Vol. 199, No. 5, 01.09.2017, p. 1635-1646.

Research output: Contribution to journalArticle

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