| First Author | Schmidt CS | Year | 2003 |
| Journal | J Exp Med | Volume | 197 |
| Issue | 1 | Pages | 51-62 |
| PubMed ID | 12515813 | Mgi Jnum | J:109341 |
| Mgi Id | MGI:3628730 | Doi | 10.1084/jem.20020617 |
| Citation | Schmidt CS, et al. (2003) Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6. J Exp Med 197(1):51-62 |
| abstractText | Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6(-/-) B cell responses both in vitro and in vivo. In vitro, DR6(-/-) B cells undergo increased proliferation in response to anti-immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative response was due, at least in part, to both increased cell division and reduced cell apoptosis when compared with wild-type B cells. Consistent with these observations, increased nuclear levels and activity of nuclear factor kappaB transcription factor, c-Rel, and elevated Bcl-x(l) expression were observed in DR6(-/-) B cells upon stimulation. In addition, DR6(-/-) B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response. DR6(-/-) mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens. This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells. |
