Journal
NATURE IMMUNOLOGY
Volume 13, Issue 2, Pages 170-180Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2194
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Funding
- Ministerio de Ciencia e Innovacion [SAF 2008-02725]
- US National Institutes of Health [R01 AI074378, P01 AI61093, U01 AI95613, P01 096187]
- European Commission [HEALTH-F2-2008-201549]
- Juan de la Cierva Program
- Instituto de Salud Carlos III
- Yerkes National Primate Research Center [P51 RR00165]
- Fondazione C. Golgi di Brescia, Associazione Immunodeficienze Primitive
- ICREA Funding Source: Custom
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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.
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