B1 cell IgE impedes B2 cell IgE-mediated parasite expulsion

Abstract

Abstract Helminth infection is known for generating large amounts of poly-specific IgE. Previously we reported that innate-like B1 cells are responsible for poly-specific IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. We showed that B1 cells make large amounts of IgE. In vitro analysis of factors critical for B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that further enhanced IgE production when IL-5 was added to culture or when the B1 source was helminth infected mice. We additionally reported that there was also a novel IL-25-induced upregulation of IgE in B1 cells isolated from helminth infected mice. Here, we report that in T cell reconstituted RAG1−/− mice further reconstituted with or without B1 cells and/or B2 cells and followed by infection with N. brasiliensis only B2-reconstituted mice had significantly reduced fecal egg production that was IgE dependent. Parasite clearance was impeded by reconstitution with B1 cells and was also IgE dependent. Helminth-induced B1 cell IgE was not specific for N. brasiliensis because it blocked mast cell degranulation to N. brasiliensis excretory secretory antigens in infected mice. The data supports a hypothesis that B1 cell IgE secretion has evolved as a protective response used by the helminth. In searching for a human B cell equivalent, we additionally identified a novel population of human tonsilar B cells that respond to IL-25 stimulation with increased proliferation and IgE production. We hypothesize that these cells may be important in generation of human poly-specific IgE.