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

Nat Immunol. 2011 Dec 25;13(2):170-80. doi: 10.1038/ni.2194.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies / immunology
  • Antibodies / metabolism
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Child
  • Communicable Diseases / immunology
  • Cytokines / immunology
  • Female
  • HIV Infections / immunology
  • Humans
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulins / biosynthesis*
  • Immunoglobulins / 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


  • Antibodies
  • Cytokines
  • IL10 protein, mouse
  • Immunoglobulins
  • Interleukin-10