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B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen.

TitleB cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen.
Publication TypeJournal Article
Year of Publication2011
AuthorsPuga, I, Cols, M, Barra, CM, He, B, Cassis, L, Gentile, M, Comerma, L, Chorny, A, Shan, M, Xu, W, Magri, G, Knowles, DM, Tam, W, Chiu, A, Bussel, JB, Serrano, S, Lorente, JAntonio, Bellosillo, B, Lloreta, J, Juanpere, N, Alameda, F, Baró, T, de Heredia, CDíaz, Torán, N, Català, A, Torrebadell, M, Fortuny, C, Cusí, V, Carreras, C, Diaz, GA, J Blander, M, Farber, C-M, Silvestri, G, Cunningham-Rundles, C, Calvillo, M, Dufour, C, Notarangelo, LDora, Lougaris, V, Plebani, A, Casanova, J-L, Ganal, SC, Diefenbach, A, Aróstegui, JIgnacio, Juan, M, Yagüe, J, Mahlaoui, N, Donadieu, J, Chen, K, Cerutti, A
JournalNat Immunol
Volume13
Issue2
Pagination170-80
Date Published2011 Dec 25
ISSN1529-2916
KeywordsAdolescent, Adult, Animals, Antibodies, B-Lymphocytes, Cells, Cultured, Child, Communicable Diseases, Cytokines, Female, HIV Infections, Humans, Immunoglobulin Class Switching, Immunoglobulins, Interleukin-10, Lupus Erythematosus, Systemic, Macaca mulatta, Male, Mice, Middle Aged, Neutrophils, Somatic Hypermutation, Immunoglobulin, Spleen, Young Adult
Abstract

Neutrophils use immunoglobulins to clear antigen, but their role in immunoglobulin production is unknown. Here we identified neutrophils around the marginal zone (MZ) of the spleen, a B cell area specialized in T cell-independent immunoglobulin responses to circulating antigen. Neutrophils colonized peri-MZ areas after postnatal mucosal colonization by microbes and enhanced their B cell-helper function after receiving reprogramming signals, including interleukin 10 (IL-10), from splenic sinusoidal endothelial cells. Splenic neutrophils induced immunoglobulin class switching, somatic hypermutation and antibody production by activating MZ B cells through a mechanism that involved the cytokines BAFF, APRIL and IL-21. Neutropenic patients had fewer and hypomutated MZ B cells and a lower abundance of preimmune immunoglobulins to T cell-independent antigens, which indicates that neutrophils generate an innate layer of antimicrobial immunoglobulin defense by interacting with MZ B cells.

DOI10.1038/ni.2194
Alternate JournalNat. Immunol.
PubMed ID22197976
PubMed Central IDPMC3262910
Grant ListP51 RR00165 / RR / NCRR NIH HHS / United States
R01 AI074378-04 / AI / NIAID NIH HHS / United States
P01 096187 / / PHS HHS / United States
U01 AI095613-01 / AI / NIAID NIH HHS / United States
P01 AI096187-01 / AI / NIAID NIH HHS / United States
R01 AI074378-05 / AI / NIAID NIH HHS / United States
U01 AI095613 / AI / NIAID NIH HHS / United States
P51 RR000165 / RR / NCRR NIH HHS / United States
P01 AI096187 / AI / NIAID NIH HHS / United States
P01 AI061093 / AI / NIAID NIH HHS / United States
R01 AI074378-06 / AI / NIAID NIH HHS / United States
P01 AI061093-08 / AI / NIAID NIH HHS / United States
U19 AI096187 / AI / NIAID NIH HHS / United States
P01 AI61093 / AI / NIAID NIH HHS / United States
R01 AI057653 / AI / NIAID NIH HHS / United States
U01 AI95613 / AI / NIAID NIH HHS / United States
R01 AI074378 / AI / NIAID NIH HHS / United States