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

Irene Puga, Montserrat Cols, Carolina M. Barra, Bing He, Linda Cassis, Maurizio Gentile, Laura Comerma, Alejo Chorny, Meimei Shan, Weifeng Xu, Giuliana Magri, Daniel M. Knowles, Wayne Tam, April Chiu, James B. Bussel, Sergi Serrano, José Antonio Lorente, Beatriz Bellosillo, Josep Lloreta, Nuria JuanpereFrancesc Alameda, Teresa Baró, Cristina Díaz De Heredia, Núria Torán, Albert Català, Montserrat Torrebadell, Claudia Fortuny, Victoria Cusí, Carmen Carreras, George A. Diaz, J. Magarian Blander, Claire Michèle Farber, Guido Silvestri, Charlotte Cunningham-Rundles, Michaela Calvillo, Carlo Dufour, Lucia Dora Notarangelo, Vassilios Lougaris, Alessandro Plebani, Jean Laurent Casanova, Stephanie C. Ganal, Andreas Diefenbach, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Nizar Mahlaoui, Jean Donadieu, Kang Chen, Andrea Cerutti

Research output: Contribution to journalArticleResearchpeer-review

452 Citations (Scopus)

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. © 2012 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)170-180
JournalNature Immunology
Volume13
Issue number2
DOIs
Publication statusPublished - 1 Feb 2012

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