Regulation of B cell function by a novel adaptor and its role in autoimmune diseases
| Project/Area Number |
17591047
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | KYUSHU UNIVERCITY |
|---|
Principal Investigator |
NIIRO Hiroaki Kyushu University, Hospital, Research Associate, 大学病院, 特任助手 (20380636)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
AKASHI Koichi Kyushu University, Hospital, Professor, 大学病院, 教授 (80380385)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Autoimmune disease / Cell and tissue / Immunology / Signal transduction / Internal medicine |
|---|
| Research Abstract |
In this study, we focus on the molecular mechanisms by which a novel adaptor Bam32 regulates B cell growth and B cell receptor (BCR) internalization, and also elucidate a role of Bam32 in the pathogenesis of autoimmune diseases.
(1) Regulation of B cell growth by Bam32
Bam32 regulates Rac activation that is critical for B cell growth. Vav2 is one of critical upstream molecules (Rac-GEF) for Rac activation. Upon B cell activation, Vav2 got tyrosine-phosphorylated and associated with Bam32. Previous studies showed that Vav2 phosphorylation is crucial for Rac activation. However, Vav2 phosphorylation was not altered in the absence of Bam32. This suggests that Bam32 regulates Vav2 function by a phosphorylation-independent mechanism.
(2) Regulation of BCR internalization by Bam32
Bam32 regulates BCR internalization in an actin-dependent manner. Dynamin 2 regulates both actin polymerization and internalization of various receptors. Upon B cell activation, dynamin 2 got phosphorylated, and the absence of Bam32 did not affect its phosphorylation. However, confocal studies showed that Bam32 clearly colocalizes with dynamin 2 upon stimulation. Moreover, membrane translocation of dynamin 2 was impaired in the absence of Bam32, suggesting that Bam32 regulates dynamin 2 function in a phosphorylation-independent manner.
(3) Role of Bam32 in the pathogenesis of autoimmune diseases
B cell growth and antigen presentation are both critical events in the pathogenesis of autoimmune disease. Since Bam32 regulates both events, it is of great interest to determine whether aberrant expression of this adaptor is associated with dysfunction of B cells in autoimmune diseases. Indeed, higher levels of Bam32 mRNA were observed in both naive and memory B cell subsets in systemic lupus erythematosus (SLE). The difference in Bam32 expression was more pronounced in memory B cells. These results suggest a pathological role of Bam32 in B cell dysfunction of autoimmune diseases such as SLE.
|
Report
(3 results)
Research Products
(15 results)
