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

Puga, Irene; Cols, Montserrat; Barra, Carolina M.; He, Bing-Yang; 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; Díaz de Heredia, Cristina; Toran, Nuria; Catala, Albert; Torrebadell, Montserrat; Fortuny, Claudia; Cusi, 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; Arostegui, Juan Ignacio; Juan, Manel; Yagüe, Jordi; Mahlaoui, Nizar; Donadieu, Jean; Chen, Kang; Cerutti, Andrea

doi:10.1038/ni.2194

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

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Author(s): Irene Puga ¹ , Montserrat Cols ² , Carolina M. Barra ¹ , Bing He ² , Linda Cassis ¹ , Maurizio Gentile ¹ , Laura Comerma ³ , Alejo Chorny ² , Meimei Shan ² , Weifeng Xu ² , Giuliana Magri ¹ , Daniel M. Knowles ⁴ , Wayne Tam ⁴ , April Chiu ⁵ , James B Bussel ⁶ , Sergi Serrano ³ , José Antonio Lorente ⁷ , Beatriz Bellosillo ³ , Josep Lloreta ³ , Nuria Juanpere ³ , Francesc Alameda ³ , Teresa Baró ³ , Cristina Díaz de Heredia ⁸ , Núria Torán ⁹ , Albert Català ¹⁰ , Montserrat Torrebadell ¹⁰ , Claudia Fortuny ¹¹ , Victoria Cusi ¹² , Carmen Carreras ¹³ , George A. Diaz ¹⁴ , J. Magarian Blander ² , Claire-Michèle Farber ¹⁵ , Guido Silvestri ¹⁶ , Charlotte Cunningham-Rundles ² , Michaela Calvillo ¹⁷ , Carlo Dufour ¹⁷ , Lucia Dora Notarangelo ¹⁸ , Vassilios Lougaris ¹⁹ , Alessandro Plebani ¹⁹ , Jean-Laurent Casanova ²⁰ ^, ²¹ , Stephanie C. Ganal ²² , Andreas Diefenbach ²² , Juan Ignacio Aróstegui ²³ , Manel Juan ²³ , Jordi Yagüe ²³ , Nizar Mahlaoui ²⁴ , Jean Donadieu ²⁵ , Kang Chen ² , Andrea Cerutti ¹ ^, ² ^, ²⁶

Publication date (Electronic): 25 December 2011

Journal: Nature Immunology

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Abstract

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

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Author and article information

Journal

Journal ID (nlm-journal-id): 100941354

Journal ID (pubmed-jr-id): 21750

Journal ID (nlm-ta): Nat Immunol

Journal ID (iso-abbrev): Nat. Immunol.

Title: Nature Immunology

ISSN (Print): 1529-2908

ISSN (Electronic): 1529-2916

Publication date Nihms-submitted: 6 December 2011

Publication date (Electronic): 25 December 2011

Publication date PMC-release: 01 August 2012

Volume: 13

Issue: 2

Pages: 170-180

Affiliations

[1 ]Institut Municipal d'Investigació Mèdica-Hospital del Mar, Barcelona, Spain

[2 ]Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA

[3 ]Department of Pathology, Hospital del Mar, Universitat Autònoma de Barcelona and Universitat Pompeu Fabra, Barcelona, Spain

[4 ]Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA

[5 ]Department of Pathology, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA

[6 ]Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA

[7 ]Department of Urology, Hospital del Mar, Barcelona, Spain

[8 ]Department of Pediatric Hematology and Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain

[9 ]Department of Pathology, Hospital Universitari Vall d'Hebron, Barcelona, Spain

[10 ]Department of Hematology, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain

[11 ]Department of Pediatrics, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain

[12 ]Department of Pathology, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain

[13 ]Children Hematology Unit, Hospital de la Fe, Valencia, Spain

[14 ]Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA

[15 ]Unit of Immunodeficiency, Hospital Erasme-ULB, Brussels, Belgium

[16 ]Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA

[17 ]Hematology Unit, G. Gaslini Children's Institute, Genova, Italy

[18 ]Oncohematology and Bone Marrow Transplantation Unit, Children's Hospital, Brescia, Italy

[19 ]Pediatric Clinic and Institute of Molecular Medicine “A. Nocivelli”,University of Brescia and Children's Hospital, Brescia, Italy

[20 ]St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA

[21 ]Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de Santé et de la Recherche Médicale U550 and Necker-Enfants Malades Medical School, Paris, France

[22 ]Institute of Medical Microbiology & Hygiene, University of Freiburg, Freiburg, Germany

[23 ]Immunology Service, Hospital Clínic of Barcelona, Barcelona, Spain

[24 ]CEREDIH, The French National Reference Center for Primary Immune Deficiencies and Paediatric Haematology-Immunolgy and Rheumatology Unit, Hôpital Necker-Enfants Malades, Paris, France

[25 ]Service d'Hémato Oncologie Pédiatrique, Registre des Neutropénies Congénitales, Hôpital Trousseau, Paris, France

[26 ]Catalan Institute for Research and Advanced Studies, Barcelona Biomedical Research Park, Barcelona, Spain

Author notes

[27]

These authors contributed equally to this work.

Correspondence should be addressed to A.C ( acerutti@ 123456imim.es or andrea.cerutti@ 123456mssm.edu ).

Article

Manuscript ID: NIHMS340279

DOI: 10.1038/ni.2194

PMC ID: 3262910

PubMed ID: 22197976

SO-VID: e4d664b3-3031-437d-a681-42c51f40e5f7

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