| First Author | Coughlin JJ | Year | 2006 |
| Journal | Immunol Lett | Volume | 105 |
| Issue | 1 | Pages | 77-82 |
| PubMed ID | 16530850 | Mgi Jnum | J:144136 |
| Mgi Id | MGI:3830158 | Doi | 10.1016/j.imlet.2006.01.005 |
| Citation | Coughlin JJ, et al. (2006) The role of RasGRPs in regulation of lymphocyte proliferation. Immunol Lett 105(1):77-82 |
| abstractText | RasGRP1 links TCR signaling to Ras in T cells, while both RasGRP1 and RasGRP3 link BCR signaling to Ras in B cells. T cells deficient in RasGRP1 have defective proliferative responses as do B cells deficient in both RasGRP1 and RasGRP3, confirming the importance of Ras activation in lymphocyte proliferation. While aged Rasgrp1-/- mice develop late-onset autoimmunity characterized by splenomegaly and the presence of anti-nuclear antibodies (ANA), the additional loss of RasGRP3 expression inhibits this phenotype. We show here that the autoimmunity in Rasgrp1-/- mice is T cell dependent. Compared to wildtype, Rasgrp1-/- T cells induce greater in vitro B cell proliferation that is due, at least in part, to increased production of interleukin-4 (IL-4). Rasgrp1 Rasgrp3 double mutant B cells are less responsive to this T cell stimulation. The reduced double mutant B cell proliferative response was paralleled by decreased induction of cyclin D2 upon stimulation with IL-4 and anti-IgM. Taken together these results suggest that double mutant mice fail to generate autoimmunity due to their decreased B cell cyclin D2 accumulation, and thus proliferation, in response to the elevated levels of IL-4 produced by mutant T cells. |
