Eosinophils regulate peripheral B cell numbers in both mice and humans

J Immunol. 2014 Apr 15;192(8):3548-58. doi: 10.4049/jimmunol.1302241. Epub 2014 Mar 10.

Abstract

The view of eosinophils (Eos) as solely effector cells involved in host parasite defense and in the pathophysiology of allergic diseases has been challenged in recent years. In fact, there is a growing realization that these cells interact with other components of innate and adaptive immunity. For example, mouse Eos were recently demonstrated to promote plasma cell retention in the bone marrow. However, it remains unknown whether Eos influence the biology of normal B lymphocytes. In this study, we specifically assessed the effect of Eos on B cell survival, proliferation, and Ig secretion. Our data first revealed that the genetic deletion of Eos from NJ1638 IL-5 transgenic hypereosinophilic mice (previously shown to display profound B cell expansion) resulted in the near abolishment of the B cell lymphocytosis. In vitro studies using human tissues demonstrated Eos' proximity to B cell follicles and their ability to promote B cell survival, proliferation, and Ig secretion via a contact-independent mechanism. Additionally, this ability of Eos to enhance B cell responsiveness was observed in both T-independent and T-dependent B cell activation and appears to be independent of the activation state of Eos. Finally, a retrospective clinical study of hypereosinophilic patients revealed a direct correlation between peripheral blood eosinophil levels and B cell numbers. Taken together, our study identifies a novel role for Eos in the regulation of humoral immunity via their impact on B cell homeostasis and proliferation upon activation.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Communication / immunology
  • Eosinophilia / blood
  • Eosinophilia / genetics
  • Eosinophilia / immunology
  • Eosinophils / physiology*
  • Humans
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism
  • Leukocyte Count
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphocytosis / blood
  • Lymphocytosis / genetics
  • Lymphocytosis / immunology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / pathology
  • Mice
  • Mice, Transgenic
  • T-Lymphocytes / immunology

Substances

  • Interleukin-5