title: FCRL regulation in innate-like B cells.
abstract: Coelomic cavity-derived B-1 and splenic marginal zone (MZ) B lymphocytes play principal roles in frontline host protection at homeostasis and during primary humoral immune responses. Although they share many features that enable rapid and broad-based defense against pathogens, these innate-like subsets have disparate B cell receptor (BCR) signaling features. Members of the Fc receptor-like (FCRL) family are preferentially expressed by B cells and possess tyrosine-based immunoregulatory function. An unusual characteristic of many of these cell surface proteins is the presence of both inhibitory (ITIM) and activating (ITAM-like) motifs in their cytoplasmic tails. In mice, FCRL5 is a discrete marker of splenic MZ and peritoneal B-1 B cells and has both ITIM and ITAM-like sequences. Recent work explored its signaling properties and identified that FCRL5 differentially influences innate-like BCR function. Closer scrutiny of these differences disclosed the ability of FCRL5 to counter-regulate BCR activation by recruiting SHP-1 and Lyn to its cytoplasmic motifs. Furthermore, the disparity in FCRL5 regulation between MZ and B-1 B cells correlated with relative intracellular concentrations of SHP-1. These findings validate and extend our understanding of the unique signaling features in innate-like B cells and provide new insight into the complexity of FCRL modulation.
authors.affiliation: Departments of Medicine, Microbiology, and Biochemistry and Molecular Genetics, and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Davis
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*
chemical_list: C452186:FCRLA protein, human; D011961:Receptors, Fc
keywords: B cells; BCR signaling; kinase; phosphatase; regulation