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PMID: 22197976 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 13 ·No. 2 ·2011-12-25 ·Pages 170-80

Puga 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 JA, Bellosillo B, Lloreta J, Juanpere N, Alameda F, Baró T, de Heredia CD, Torán N, Català A, Torrebadell M, Fortuny C, Cusí V, Carreras C, Diaz GA, Blander JM, Farber CM, Silvestri G, Cunningham-Rundles C, Calvillo M, Dufour C, Notarangelo LD, Lougaris V, Plebani A, Casanova JL, Ganal SC, Diefenbach A, Aróstegui JI, Juan M, Yagüe J, Mahlaoui N, Donadieu J, Chen K, Cerutti A

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.

MeSH Terms
Adolescent Adult Animals Antibodies/immunology,metabolism B-Lymphocytes/immunology Cells, Cultured Child Communicable Diseases/immunology Cytokines/immunology Female HIV Infections/immunology Humans Immunoglobulin Class Switching/immunology Immunoglobulins/biosynthesis,immunology Interleukin-10/immunology Lupus Erythematosus, Systemic/immunology Macaca mulatta/immunology Male Mice Middle Aged Neutrophils/immunology Somatic Hypermutation, Immunoglobulin/immunology Spleen/immunology Young Adult
Chemicals
Antibodies Cytokines IL10 protein, mouse Immunoglobulins Interleukin-10
Authors & Affiliations
49 authors, click to expand affiliations / ORCID
Puga Irene
Institut Municipal d'Investigació Mèdica-Hospital del Mar, Barcelona, Spain.
Cols Montserrat
Barra Carolina M
He Bing
Cassis Linda
Gentile Maurizio
Comerma Laura
Chorny Alejo
Shan Meimei
Xu Weifeng
Magri Giuliana
Knowles Daniel M
Tam Wayne
Chiu April
Bussel James B
Serrano Sergi
Lorente José Antonio
Bellosillo Beatriz
Lloreta Josep
Juanpere Nuria
Alameda Francesc
Baró Teresa
de Heredia Cristina Díaz
Torán Núria
Català Albert
Torrebadell Montserrat
Fortuny Claudia
Cusí Victoria
Carreras Carmen
Diaz George A
Blander J Magarian
Farber Claire-Michèle
Silvestri Guido
Cunningham-Rundles Charlotte
Calvillo Michaela
Dufour Carlo
Notarangelo Lucia Dora
Lougaris Vassilios
Plebani Alessandro
Casanova Jean-Laurent
Ganal Stephanie C
Diefenbach Andreas
Aróstegui Juan Ignacio
Juan Manel
Yagüe Jordi
Mahlaoui Nizar
Donadieu Jean
Chen Kang
Cerutti Andrea
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2194
Published
2011-12-25
Epub
2011-00-25
Pages
170-80
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3262910
Subset
IM
Grants
NCRR NIH HHS · P51 RR00165 · United States
NIAID NIH HHS · R01 AI074378-04 · United States
PHS HHS · P01 096187 · United States
NIAID NIH HHS · U01 AI095613-01 · United States
NIAID NIH HHS · P01 AI096187-01 · United States
NIAID NIH HHS · R01 AI074378-05 · United States
NIAID NIH HHS · U01 AI095613 · United States
NCRR NIH HHS · P51 RR000165 · United States
NIDDK NIH HHS · P01 DK072201 · United States
NIAID NIH HHS · P01 AI061093-08 · United States
NIAID NIH HHS · U01 AI95613 · United States
NIAID NIH HHS · R01 AI074378 · United States
NIAID NIH HHS · P01 AI061093 · United States
NIAID NIH HHS · R01 AI074378-06 · United States
NIAID NIH HHS · U19 AI096187 · United States
NIAID NIH HHS · P01 AI61093 · United States
NIAID NIH HHS · R01 AI057653 · United States
Corrections
ErratumIn
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CommentIn
PMID: 22261958
CommentIn
PMID: 22266690
External Links
PubMed source DOI: 10.1038/ni.2194 PMC Full Text View journal details
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