sIgM-FcμR Interactions Regulate Early B Cell Activation and Plasma Cell Development after Influenza Virus Infection

Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the splice region ( ) 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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2017-09, Vol.199 (5), p.1635-1646
Main Authors: Nguyen, Trang T T, Graf, Beth A, Randall, Troy D, Baumgarth, Nicole
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - immunology
B-Lymphocytes - virology
Bone marrow
Cell activation
Cell Differentiation
Clonal deletion
Complement activation
Female
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinins
Humoral immunity
Immunity, Humoral
Immunoglobulin Constant Regions - metabolism
Immunoglobulin G
Immunoglobulin M
Immunoglobulin mu-Chains - metabolism
Immunological memory
Infections
Influenza
Lymphocyte Activation
Lymphocyte receptors
Lymphocytes B
Male
Memory cells
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae - immunology
Orthomyxoviridae Infections - immunology
Plasma cells
Plasma Cells - immunology
Plasma Cells - virology
Protein Binding
Receptors, Fc - genetics
Receptors, Fc - metabolism
Spleen
T cell receptors
Viruses
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Summary:Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the splice region ( ) 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 μs-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 FcμR expression on B cells, but not lack of Fcα/μR expression or complement activation, reduced antiviral IgG responses to the same extent as observed in μs mice. B cell-specific 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 μs but not B cells, as demonstrated with mixed bone marrow chimeric mice. Taken together, the data suggest that sIgM interacts with FcμR on B cells to support early B cell activation and the development of long-lived humoral immunity.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1700560