Th103 - Histamine Receptors Control B Cell Germinal Center Responses and Production of Antigen-specific Ige

Tania Velez – University of Virginia; Julie Swartzendruber – Midwest University; Krishan Chhiba – Northwestern University; Rebecca Krier-Burris – Northwestern University; Joshua Wechsler – Lurie Childrens Hospital; Kristin Erickson – Northwestern University; Kathryn Hulse – Seeker Bio

Abstract Text: Histamine is a potent downstream mediator in allergic reactions, and yet histamine receptors are also expressed on cells important for the development of allergic immunity, including T cells, dendritic cells, and B cells. Previous studies in animal models have demonstrated that histamine alters antibody production via Histamine Receptor 4 (H4R) on dendritic cells or H1R and H2R on T cells, but direct regulation of B cells by histamine is unclear. Here, we demonstrate that human and mouse B cells express H1R and H2R and that both receptors are required for competent specific antibody production to in vivo immunization with ovalbumin. The strongest impact was exerted over the regulation of IgE, with deficiency in both H1R and H2R rendering a complete loss of specific IgE and poor germinal center formation. B cell subsets were largely unaffected in H1R/H2R deficient mice, and adoptive transfer of congenic cells into immunodeficient recipients established that histamine exerts effects on both the B and T compartments for optimal induction of IgE responses in vivo. A B cell intrinsic defect in IgE was observed in H1R/H2R deficient B cells using in vitro assays of IgE production, and molecular analysis of these B cells showed defects in expression of genes involved in the germinal center response and cell survival. Collectively, these findings support a role for histamine, released during IgE-mediated activation, in regulating the further development of IgE and antigen-specific antibodies and sustaining the allergic phenotype.