林恩
免疫受体酪氨酸激活基序
生物
断点群集区域
细胞生物学
锡克
B细胞受体
受体
信号转导
Src家族激酶
原癌基因酪氨酸蛋白激酶Src
蛋白质酪氨酸磷酸酶
SH2域
酪氨酸
先天免疫系统
B细胞
酪氨酸激酶
免疫学
遗传学
生物化学
抗体
作者
Zilu Zhu,Ran Li,Hao Li,Tong Zhou,Randall S. Davis
标识
DOI:10.1073/pnas.1215156110
摘要
Innate-like splenic marginal zone (MZ) and peritoneal cavity B1 B lymphocytes share critical responsibilities in humoral responses but have divergent B-cell receptor (BCR) signaling features. A discrete marker of these subsets with tyrosine-based dual regulatory potential termed “Fc receptor-like 5” (FCRL5) was investigated to explore this discrepancy. Although FCRL5 repressed the robust BCR activity that is characteristic of MZ B cells, it had no influence on antigen receptor stimulation that is blunted in peritoneal cavity-derived B1 B cells. The molecular basis for the receptor’s inhibitory function derived from recruitment of the Src homology-2 domain-containing tyrosine phosphatase 1 (SHP-1) to a cytoplasmic immunoreceptor tyrosine-based inhibitory motif. Surprisingly, mutagenesis of this docking site unearthed coactivation properties for FCRL5 that were orchestrated by independent association of the Lyn Src-family kinase with an intracellular immunoreceptor tyrosine-based activation motif-like sequence. FCRL5’s unique binary regulation directly correlated with SHP-1 and Lyn activity, which, like BCR function, differed between MZ and B1 B cells. These findings collectively imply a specialized counterregulatory role for FCRL molecules at the intersection of innate and adaptive immunity.
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