FCRL regulation in innate‐like B cells. Issue 1 (11th May 2015)

• Record Type: Journal Article
• Authors: Davis, Randall S.
• Other Names: Rothstein Thomas L. guestEditor.; Herzenberg Leonore A. guestEditor.; Holodick Nichol E. guestEditor.; Ghosn Eliver guestEditor.
• Is Part Of: Annals of the New York Academy of Sciences. Volume 1362:Issue 1(2015)
• Page Start: 110
• Page End: 116
• Publication Date: 2015-05-11
• Subjects: B cells -- BCR signaling -- regulation -- kinase -- phosphatase; Medical sciences -- Periodicals; Medicine -- Periodicals; Science -- Periodicals; 610
• DOI: 10.1111/nyas.12771
• Languages: English
• ISSNs: 0077-8923

Abstract

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.