The mechanism by which Fc Receptor Like-1(FcRL1) enhances B cell receptor-induced activation

• Main Authors: Tsung-Han Hsieh, 謝宗翰
• Other Authors: Chuen-Miin Leu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/78316950068928613907

碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 97 === Fc receptor-like proteins (FcRLs) are a group of receptors that have homologous sequence to the classical Fc receptors. Eight human FcRLs have been identified: FcRL1-6, FcRLA and FcRLB. FcRL1-6 are transmembrane proteins; FcRLA and FcRLB are expressed in the cytoplasm. All FcRLs except FcRL6 are expressed by B cells. Human FcRL1 has 3 extracellular immunoglobulin-like domains, a negative charged glutamic acid in the transmembrane domain, and 2 ITAM-like motifs in the cytoplasmic region. Previous study has demonstrated that human FcRL1 is an activation receptor on B cells, and it can enhance BCR-induced activation. To study the mechanism by which human FcRL1 enhances BCR-induced activation, we first examined whether FcRL1 associates with BCR coreceptor CD19 because of the co-expression FcRL1 and CD19 in B cells. Furthermore, a glutamic acid in the transmembrane domain of FcRL1 may associate with the positive charged histidine in the transmembrane domain of CD19. Our biochemical results demonstrated that HA-FcRL1 could be specifically co-immunopreciptated with CD19, but not with an non-related surface receptor CD71 in a 293T overexpression system. In addition, neither the glutamic acid in transmembrane domain nor the intracellular region of FcRL1 was essential for the association. The partial co-localization of FcRL1 and CD19 was seen on the surface of transfected 293T cells by immunofluorescence microscopy. Our signaling analysis in B cells showed that tyrosine phosphorylation of CD19 was dramatically increased after FcRL1 co-ligation with surface IgM. Consistent with this finding, the recruitment and phosphorylation of phosphatidylinositol 3’-kinase (PI3K) was significantly enhanced by FcRL1 co-ligation. However, the total protein tyrosine phosphorylation and ERK activation were not affected. Collectively, our result suggest that FcRL1 co-ligation upregulated CD19 phosphorylation, followed by the activation of PI3K. FcRL1 may act as a co-receptor in the BCR signaling.