Helminth-induced B1 IgE is protective against allergic disease.

Abstract Helminth infection is well known for its ability to generate large amounts of non-specific IgE. This hinders the parasite-specific IgE thereby reducing mast cell (MC) degranulation and anti-helminth immunity. This study shows that the innate-like B1 cells are responsible for the substantial amounts of IgE induced during the Th2 helminth infection, Nippostrongylus brasiliensis (Nb). We utilize a mouse model with defects in hematopoiesis that results in loss of B2 cells, but retains normal B1 development, the ADAM10 transgenic mouse. These mice have equivalent IgE production in Nb when compared to wild type (WT) controls that is T cell dependent. Utilizing the NP-KLH system, we demonstrate that these mice make no antigen-specific IgG1, either high or total affinity. They additionally make no increased overall antibody when boosted with the same antigen. In WT mice, we show a population of B1 plasma cells (CD11b+CD23−B220intCD138+) in vivo, that express secreted IgE message during Nb infection. We additionally show that B1 cells (CD11b+CD23−B220int) sorted from naïve and Nb infected mice make large amounts of IgE in in vitro culture with IL-4, anti-CD40, and IL-5 by ELISA and secreted IgE message by RT-PCR. These B1 cells become CD138+ after 5 days of culture. Finally and most importantly, we show that B1 IgE is first unable to induce MC degranulation in an active cutaneous anaphylaxis model and second, it can block MC degranulation in a model of passive cutaneous anaphylaxis. Overall, these data represents a protective response that has evolved for the helminth, where non-specific B1 IgE blocks MC degranulation and thereby protects the helminth from damage. Excitingly, this could be harnessed as a potential protection against allergic disease.