Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Immunol. 2010 Dec 15;185(12):7405-12. doi: 10.4049/jimmunol.1002305. Epub 2010 Nov 10.
FcR-like (FCRL) 2 is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus ITIMs in addition to a putative ITAM sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and analyzed its functional potential to show that coligation with the BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-containing phosphatase-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are required for complete inhibition of BCR signaling, whereas tyrosines in the putative activation motif are dispensable for signal modulation. These findings suggest a negative immunomodulatory function for FCRL2 in the regulation of memory B cells.
FcR 样蛋白 2（FCRL2）是一种具有免疫调节潜能的跨膜蛋白，其在人类中优先表达于记忆 B 细胞。它的胞质域中除了一个假定的 ITAM 序列外，还有两个 ITIM 共有序列。我们已经证实了 FCRL2 的细胞分布，并分析了其功能潜力，结果表明与 BCR 的交联导致其 ITIM 基序的酪氨酸磷酸化，随后 Src 同源结构域 2 结构域含有磷酸酶-1 的募集，从而促进 BCR 信号的抑制。突变分析表明，FCRL2 的两个抑制基序中的酪氨酸残基对于完全抑制 BCR 信号都是必需的，而假定的激活基序中的酪氨酸残基对于信号调节是可有可无的。这些发现表明 FCRL2 在调节记忆 B 细胞方面具有负免疫调节功能。
