| First Author | Jeelall YS | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 11 | Pages | 1907-17 |
| PubMed ID | 23027925 | Mgi Jnum | J:190942 |
| Mgi Id | MGI:5450782 | Doi | 10.1084/jem.20112744 |
| Citation | Jeelall YS, et al. (2012) Human lymphoma mutations reveal CARD11 as the switch between self-antigen-induced B cell death or proliferation and autoantibody production. J Exp Med 209(11):1907-17 |
| abstractText | Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewiring of the signaling apparatus or if it can arise from a single molecular change. By introducing individual CARD11 mutations found in human lymphomas into antigen-activated mature B lymphocytes in mice, we find here that lymphoma-derived CARD11 mutations switch the effect of self-antigen from inducing B cell death into T cell-independent proliferation, Blimp1-mediated plasmablast differentiation, and autoantibody secretion. Our findings demonstrate that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells and that mutations in this switch represent a powerful initiator for aberrant B cell responses in vivo. |
