B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade

Publication date: 13 February 2018
Source:Cell Reports, Volume 22, Issue 7
Author(s): Rebecca K. Martin, Sheela R. Damle, Yolander A. Valentine, Matthew P. Zellner, Briana N. James, Joseph C. Lownik, Andrea J. Luker, Elijah H. Davis, Martha M. DeMeules, Laura M. Khandjian, Fred D. Finkelman, Joseph F. Urban, Daniel H. Conrad
Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1^−/− mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth.

Graphical abstract

Teaser

Martin et al. show that B1 cell IgE is induced during Th2 helminth infections by IL-25. This B1 cell IgE blocks parasite clearance through inhibition of mucosal mast cell activation by B2 cell IgE.


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