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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.

SUBMITTER: Puga I 

PROVIDER: S-EPMC3262910 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Puga Irene I   Cols Montserrat M   Barra Carolina M CM   He Bing B   Cassis Linda L   Gentile Maurizio M   Comerma Laura L   Chorny Alejo A   Shan Meimei M   Xu Weifeng W   Magri Giuliana G   Knowles Daniel M DM   Tam Wayne W   Chiu April A   Bussel James B JB   Serrano Sergi S   Lorente José Antonio JA   Bellosillo Beatriz B   Lloreta Josep J   Juanpere Nuria N   Alameda Francesc F   Baró Teresa T   de Heredia Cristina Díaz CD   Torán Núria N   Català Albert A   Torrebadell Montserrat M   Fortuny Claudia C   Cusí Victoria V   Carreras Carmen C   Diaz George A GA   Blander J Magarian JM   Farber Claire-Michèle CM   Silvestri Guido G   Cunningham-Rundles Charlotte C   Calvillo Michaela M   Dufour Carlo C   Notarangelo Lucia Dora LD   Lougaris Vassilios V   Plebani Alessandro A   Casanova Jean-Laurent JL   Ganal Stephanie C SC   Diefenbach Andreas A   Aróstegui Juan Ignacio JI   Juan Manel M   Yagüe Jordi J   Mahlaoui Nizar N   Donadieu Jean J   Chen Kang K   Cerutti Andrea A  

Nature immunology 20111225 2


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 sinusoid  ...[more]

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