| First Author | Browne CD | Year | 2009 |
| Journal | Immunity | Volume | 31 |
| Issue | 5 | Pages | 749-60 |
| PubMed ID | 19896393 | Mgi Jnum | J:155314 |
| Mgi Id | MGI:4413497 | Doi | 10.1016/j.immuni.2009.08.026 |
| Citation | Browne CD, et al. (2009) Suppression of phosphatidylinositol 3,4,5-trisphosphate production is a key determinant of B cell anergy. Immunity 31(5):749-60 |
| abstractText | Anergy is a critical physiologic mechanism to sensor self-reactive B cells. However, a biochemical understanding of how anergy is achieved and maintained is lacking. Herein, we investigated the role of the phosphoinositide 3-kinase (PI3K) lipid product PI(3,4,5)P(3) in B cell anergy. We found reduced generation of PI(3,4,5)P(3) in anergic B cells, which was attributable to reduced phosphorylation of the PI3K membrane adaptor CD19, as well as increased expression of the inositol phosphatase PTEN. Sustained production of PI(3,4,5)P(3) in B cells, achieved through conditional deletion of Pten, resulted in failed tolerance induction and abundant autoantibody production. In contrast to wild-type immature B cells, B cell receptor engagement of PTEN-deficient immature B cells resulted in activation and proliferation, indicating a central defect in early B cell responsiveness. These findings establish repression of the PI3K signaling pathway as a necessary condition to avert the generation, activation, and persistence of self-reactive B cells. |
