title: B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen.
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.
authors.affiliation: Institut Municipal d'Investigació Mèdica-Hospital del Mar, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Puga
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cols
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Barra
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Linda
authors.initials: L
authors.lastname: Cassis
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gentile
authors.forename: Laura
authors.initials: L
authors.lastname: Comerma
authors.forename: Alejo
authors.initials: A
authors.lastname: Chorny
authors.forename: Meimei
authors.initials: M
authors.lastname: Shan
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Giuliana
authors.initials: G
authors.lastname: Magri
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Lorente
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Nuria
authors.initials: N
authors.lastname: Juanpere
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
authors.forename: Teresa
authors.initials: T
authors.lastname: Baró
authors.forename: Cristina Díaz
authors.initials: CD
authors.lastname: de Heredia
authors.forename: Núria
authors.initials: N
authors.lastname: Torán
authors.forename: Albert
authors.initials: A
authors.lastname: Català
authors.forename: Montserrat
authors.initials: M
authors.lastname: Torrebadell
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Victoria
authors.initials: V
authors.lastname: Cusí
authors.forename: Carmen
authors.initials: C
authors.lastname: Carreras
authors.forename: George A
authors.initials: GA
authors.lastname: Diaz
authors.forename: J Magarian
authors.initials: JM
authors.lastname: Blander
authors.forename: Claire-Michèle
authors.initials: CM
authors.lastname: Farber
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
authors.forename: Michaela
authors.initials: M
authors.lastname: Calvillo
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Lucia Dora
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Ganal
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Aróstegui
authors.forename: Manel
authors.initials: M
authors.lastname: Juan
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D003141:Communicable Diseases / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D013154:Spleen / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D016207:Cytokines; C556062:IL10 protein, mouse; D007136:Immunoglobulins; D016753:Interleukin-10