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

• Type of Material: Article
• Authors: Irene Puga, Hospital del Mar; Montserrat Cols, Mount Sinai School of Medicine; Carolina M. Barra, Hospital del Mar; Bing He, Mount Sinai School of Medicine; Linda Cassis, Hospital del Mar; Maurizio Gentile, Hospital del Mar; Laura Comerma, Universitat Autònoma de Barcelona; Alejo Chorny, Mount Sinai School of Medicine; Meimei Shan, Mount Sinai School of Medicine; Weifeng Xu, Mount Sinai School of Medicine; Giuliana Magri, Hospital del Mar; Daniel M. Knowles, Cornell University; Wayne Tam, Cornell University; April Chiu, Harvard University; James B Bussel, Weill Cornell Medical College; Sergi Serrano, Universitat Autònoma de Barcelona; Jose Antonio Lorente, Hospital del Mar; Beatriz Bellosillo, Universitat Autònoma de Barcelona; Josep Lloreta, Universitat Autònoma de Barcelona; Guido Silvestri, Emory University
• Language: English
• Date: 2012-02-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ni.2194
• Title of Journal or Parent Work: Nature Immunology
• ISSN: 1529-2908
• Volume: 13
• Issue: 2
• Start Page: 170
• End Page: 180
• Grant/Funding Information: Supported by Ministerio de Ciencia e Innovación grant SAF 2008-02725 to A. Cerutti; US National Institutes of Health grants R01 AI074378, P01 AI61093, U01 AI95613 and P01 096187 to A. Cerutti; EUROPADnet HEALTH-F2-2008-201549 to A. Cerutti; Juan de la Cierva post-doctoral fellowships to I.P. and G.M.; Sara Borrell post-doctoral fellowship to A. Chorny; pre-doctoral fellowships from the Instituto de Salud Carlos III and Ministerio de Ciencia e Innovación to C.B and M.G.; Yerkes base grant P51 RR00165 to G.S.; and Fondazione C. Golgi di Brescia, Associazione Immunodeficienze Primitive to A. Plebani.
• Keywords: SOMATIC HYPERMUTATION; Immunology; Life Sciences & Biomedicine; DEGRADATION; Science & Technology; MEMORY; CLASS SWITCH RECOMBINATION; ACTIVATION; INFLAMMATORY RESPONSES; RECEPTOR; APRIL; COMMENSAL BACTERIA; ANTIBODY-RESPONSES
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

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.