B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade
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, Jr.,
Daniel H. Conrad
Affiliations
Rebecca K. Martin
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Sheela R. Damle
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Yolander A. Valentine
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Matthew P. Zellner
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Briana N. James
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Joseph C. Lownik
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Center for Clinical and Translational Research, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Andrea J. Luker
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Elijah H. Davis
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Martha M. DeMeules
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; University of Wisconsin-Madison, Madison, WI 53715, USA
Laura M. Khandjian
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Fred D. Finkelman
Division of Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Medicine Service, Veterans Administration Medical Center, Cincinnati, OH, USA
Joseph F. Urban, Jr.
United States Department of Agriculture, Agricultural Research Service, Diet, Genomics and Immunology Laboratory, Beltsville, MD 20705, USA
Daniel H. Conrad
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Corresponding author
Summary: 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.
