| RRC ID |
37680
|
| 著者 |
Kochi Y, Myouzen K, Yamada R, Suzuki A, Kurosaki T, Nakamura Y, Yamamoto K.
|
| タイトル |
FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling.
|
| ジャーナル |
J Immunol
|
| Abstract |
A polymorphism that up-regulates the expression of Fc receptor-like 3 (FCRL3) gene has recently been described as predisposing for several human autoimmune diseases. FCRL3 is preferentially expressed on B cells and is unique in displaying both an ITAM and an ITIM in the cytosolic domain, suggesting signaling functions. Herein, we show that FCRL3 potentially inhibits BCR-mediated signaling, using murine FcgammaRIIB/human FCRL3 chimeric protein. Coligation of the chimeric protein with BCR leads to phosphorylation of tyrosine residues in the cytosolic domain. This coligation inhibits cell tyrosine phosphorylation and calcium mobilization in addition to activation-induced cell death mediated by BCR signaling. Mutational analysis showed the tyrosine residues in two potential ITIMs at 662 and 692 offer the main contributions to this inhibition, which is further supported by strong associations of SH-2 domain-containing phosphatases with the following phosphotyrosine motifs: SHIP with the ITIM-like motif at 662; and SHP-1 and -2 with the canonical ITIM at 692. These results, together with previous genetic data, suggest that augmented inhibition of BCR-mediated signaling by FCRL3 with the disease-risk genotype alter the activation threshold and promote tolerance breakdown in B cells.
|
| 巻・号 |
183(9)
|
| ページ |
5502-10
|
| 公開日 |
2009-11-1
|
| DOI |
10.4049/jimmunol.0901982
|
| PII |
183/9/5502
|
| PMID |
19843936
|
| MeSH |
Amino Acid Sequence
Animals
Autoimmune Diseases / genetics
Autoimmune Diseases / metabolism*
Autoimmune Diseases / pathology
B-Lymphocyte Subsets / immunology
B-Lymphocyte Subsets / metabolism
B-Lymphocyte Subsets / pathology
Cell Line
Cell Line, Tumor
Chickens
Genetic Predisposition to Disease / genetics
Humans
Immune Tolerance / genetics
Jurkat Cells
Mice
Molecular Sequence Data
Receptors, Antigen, B-Cell / antagonists & inhibitors*
Receptors, Antigen, B-Cell / physiology*
Receptors, Immunologic / genetics*
Receptors, Immunologic / physiology
Signal Transduction / genetics
Signal Transduction / immunology*
|
| IF |
4.886
|
| 引用数 |
56
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
DT40(RCB1464) |
