Central disruption of fusional amplitude.

Abstract

FCRL1 is a tyrosine-phosphorylated receptor found on the surface of B cells and some dendritic cells. FCRL1 co-localizes with BCR signaling complexes following BCR engagement and augments BCR-induced calcium flux. By examination of phosphotyrosine-dependent interactions of FCRL1 with intracellular signaling partners, we have identified interactions between FCRL1-Tyr281 and GRAP, GRB2, SHIP-1, and SOS1, with a requirement for GRB2 to mediate binding of FCRL1 to SHIP-1 and SOS1. Examination of MAP kinase signaling downstream of FCRL1 revealed that FCRL1 suppresses ERK phosphorylation in B cells at a resting state and following BCR engagement. In vivo, naïve FCRL1 knockout mice accumulate more B cells in the spleen, including immature, follicular and marginal zone cells, implicating a potential role for FCRL1 in B cell selection and maturation. By contrast, after immunization with thymus-dependent and independent antigens, FCRL1 knockout mice show impaired production of antigen-specific antibodies indicating an essential role for FCRL1 in humoral immune responses.