Eosinophils Regulate Peripheral B Cell Numbers in Both Mice and Humans

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 immunoglobulin 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 immunoglobulin secretion via a contact-independent mechanism(s). 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 Eos’ activation state. Finally, a retrospective clinical study of hypereosinophilic patients revealed for the first time 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.

Eosinophils Mediate Protective Immunity against Secondary Nematode Infection

“…Eosinophils have been demonstrated to be required for long-term maintenance of plasma cells in the bone marrow (41, 42). We tested whether eosinophils influence numbers of plasma cells or the quantity and qualities of antibodies produced during T. spiralis infection.…”

Functions of tissue-resident eosinophils

“…Adjuvant-elicited eosinophils express IL-4, IL-6, IL-10, TNF and the plasma cell survival factor APRIL 128 and are required for early alum-induced activation of B cells and the production of antigen-specific IgM 127 . In both mice and humans, eosinophils also support increased numbers of peripheral B cells 129 ; and in mice, eosinophils promote B cell survival, proliferation and immunoglobulin secretion by a contact-independent mechanism 129 .…”

Eosinophils in Helminth Infection: Defenders and Dupes

“…Using adoptive transfer protocols in eosinophil-ablated recipient mice, it was shown that plasma cell survival is further enhanced when eosinophils are first activated with adjuvant [60], consistent with a role for eosinophils in bone marrow plasma cell survival during infection. Eosinophils are also capable of regulating peripheral B cell homeostasis and proliferation in mice [61]. Although eosinophils are dispensable for the parasite-specific IgM response during primary infection by Strongyloides stercoralis [62], they are required for production of specific IgG2c in Trichinella infection [45].…”