| First Author | Ishida D | Year | 2006 |
| Journal | Immunity | Volume | 24 |
| Issue | 4 | Pages | 417-27 |
| PubMed ID | 16618600 | Mgi Jnum | J:113348 |
| Mgi Id | MGI:3665502 | Doi | 10.1016/j.immuni.2006.02.007 |
| Citation | Ishida D, et al. (2006) Rap1 signal controls B cell receptor repertoire and generation of self-reactive B1a cells. Immunity 24(4):417-27 |
| abstractText | We previously reported that the mice deficient for SPA-1, a Rap1 GTPase-activating protein, developed hematopoietic stem cell disorders. Here, we demonstrate that SPA-1(-/-) mice show an age-dependent increase in B220(high) B1a cells producing anti-dsDNA antibody and lupus-like nephritis. SPA-1(-/-) peritoneal B1 cells revealed the altered Vkappa gene repertoire, including skewed Vkappa4 usage and the significant Igkappa/Iglambda isotype inclusion indicative of extensive receptor editing. Rap1GTP induced OcaB gene activation via p38MAPK-dependent Creb phosphorylation, and consistently, SPA-1(-/-) immature BM B cells showing high Rap1GTP exhibited the augmented expression of OcaB and Vkappa4 genes. SPA-1(-/-) BM cells could transfer the autoimmunity in association with the generation of peritoneal B220(high) B1a cells in Rag-2(-/-) recipients. Finally, a portion of SPA-1(-/-) mice developed B1 cell leukemia with hemolytic autoantibody. Present results suggest that the regulated Rap1 signal in the immature B cells plays a role in modifying the B cell receptor repertoire and in maintaining the self-tolerance. |
