| First Author | Misra RS | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 8 | Pages | 1775-89 |
| PubMed ID | 20624888 | Mgi Jnum | J:163474 |
| Mgi Id | MGI:4822086 | Doi | 10.1084/jem.20092735 |
| Citation | Misra RS, et al. (2010) Galphaq-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity. J Exp Med 207(8):1775-89 |
| abstractText | Survival of mature B cells is regulated by B cell receptor and BAFFR-dependent signals. We show that B cells from mice lacking the G(alphaq) subunit of trimeric G proteins (Gnaq(-/-) mice) have an intrinsic survival advantage over normal B cells, even in the absence of BAFF. Gnaq(-/-) B cells develop normally in the bone marrow but inappropriately survive peripheral tolerance checkpoints, leading to the accumulation of transitional, marginal zone, and follicular B cells, many of which are autoreactive. Gnaq(-/-) chimeric mice rapidly develop arthritis as well as other manifestations of systemic autoimmune disease. Importantly, we demonstrate that the development of the autoreactive B cell compartment is the result of an intrinsic defect in Gnaq(-/-) B cells, resulting in the aberrant activation of the prosurvival factor Akt. Together, these data show for the first time that signaling through trimeric G proteins is critically important for maintaining control of peripheral B cell tolerance induction and repressing autoimmunity. |
