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

I Puga, M Cols, CM Barra, B He, L Cassis… - Nature …, 2012 - nature.com
I Puga, M Cols, CM Barra, B He, L Cassis, M Gentile, L Comerma, A Chorny, M Shan, W Xu…
Nature immunology, 2012nature.com
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 …
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.
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