Davis Randall S
Departments of Medicine, Microbiology, and Biochemistry and Molecular Genetics, and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
Ann N Y Acad Sci. 2015 Dec;1362(1):110-6. doi: 10.1111/nyas.12771. Epub 2015 May 11.
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.
体腔来源的B-1细胞和脾脏边缘区（MZ）B淋巴细胞在稳态和初次体液免疫反应期间的一线宿主保护中发挥着主要作用。尽管它们具有许多能够对病原体进行快速和广泛防御的共同特征，但这些固有样亚群具有不同的B细胞受体（BCR）信号特征。Fc受体样（FCRL）家族成员在B细胞中优先表达，并具有基于酪氨酸的免疫调节功能。这些细胞表面蛋白中的许多蛋白的一个不寻常特征是其胞质尾部同时存在抑制性（ITIM）和激活性（ITAM样）基序。在小鼠中，FCRL5是脾脏MZ和腹膜B-1 B细胞的离散标志物，并且具有ITIM和ITAM样序列。最近的研究探讨了其信号特性，并确定FCRL5对固有样BCR功能有不同影响。对这些差异的进一步研究揭示了FCRL5通过将SHP-1和Lyn募集到其胞质基序来反调节BCR激活的能力。此外，MZ和B-1 B细胞之间FCRL5调节的差异与SHP-1的相对细胞内浓度相关。这些发现验证并扩展了我们对固有样B细胞独特信号特征的理解，并为FCRL调节的复杂性提供了新的见解。
