FCRL regulation in innate-like B cells.
FCRL regulation in innate-like B cells.
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DOI：
10.1111/nyas.12771
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发表时间：
2015-12
影响因子：
5.2
通讯作者：
Davis RS
中科院分区：
文献类型：
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作者：
Davis RS
体腔来源的B-1和脾边缘区（MZ）B淋巴细胞在体内平衡和原发性体液免疫应答期间的一线宿主保护中发挥主要作用。虽然它们具有许多共同的特征，能够快速和广泛地防御病原体，但这些先天样亚群具有不同的B细胞受体（BCR）信号传导特征。Fc受体样（FCRL）家族成员优先由B细胞表达，并具有基于酪氨酸的免疫调节功能。许多这些细胞表面蛋白质的一个不寻常的特征是在它们的细胞质尾部存在抑制性（ITIM）和激活性（ITAM样）基序。在小鼠中，FCRL 5是脾MZ和腹膜B-1 B细胞的离散标记物，并且具有ITIM和ITAM样序列。最近的工作探索了它的信号传导特性，并确定FCRL 5差异影响先天性BCR功能。对这些差异的仔细研究揭示了FCRL 5通过将SHP-1和林恩募集到其细胞质基序来反调节BCR活化的能力。此外，MZ和B-1 B细胞之间FCRL 5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先天性B细胞中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。
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.