Title | Cutting Edge: Neutrophil Complement Receptor Signaling Is Required for BAFF-Dependent Humoral Responses in Mice. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Cumpelik A, Cody E, Yu SMon-Wei, Grasset EK, Dominguez-Sola D, Cerutti A, Heeger PS |
Journal | J Immunol |
Volume | 210 |
Issue | 1 |
Pagination | 19-23 |
Date Published | 2023 Jan 01 |
ISSN | 1550-6606 |
Keywords | Animals, B-Lymphocytes, Complement System Proteins, Immunoglobulin A, Mice, Mice, Knockout, Neutrophils, Receptors, Complement |
Abstract | T cell-independent (TI) B cell responses to nonprotein Ags involve multiple cues from the innate immune system. Neutrophils express complement receptors and activated neutrophils can release BAFF, but mechanisms effectively linking neutrophil activation to TI B cell responses are incompletely understood. Using germline and conditional knockout mice, we found that TI humoral responses involve alternative pathway complement activation and neutrophil-expressed C3a and C5a receptors (C3aR1/C5aR1) that promote BAFF-dependent B1 cell expansion and TI Ab production. Conditional absence of C3aR1/C5aR1 on neutrophils lowered serum BAFF levels, led to fewer Peyer's patch germinal center B cells, reduced germinal center B cells IgA class-switching, and lowered fecal IgA levels. Together, the results indicate that sequential activation of complement on neutrophils crucially supports humoral TI and mucosal IgA responses through upregulating neutrophil production of BAFF. |
DOI | 10.4049/jimmunol.2200410 |
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Alternate Journal | J Immunol |
PubMed ID | 36454023 |
PubMed Central ID | PMC9780177 |
Grant List | R01 AI141434 / AI / NIAID NIH HHS / United States T32 AI078892 / AI / NIAID NIH HHS / United States T32 DK007757 / DK / NIDDK NIH HHS / United States |