Human lymphoma mutations reveal CARD11 as the switch between self-antigen-induced B cell death or proliferation and autoantibody production
Yogesh S Jeelall, James Q Wang, Hsei-Di Law, Heather Domaschenz, Herman KH Fung, Axel Kallies, Stephen L Nutt, Christopher C Goodnow, Keisuke Horikawa
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2012
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, ..View full abstract
Y.S. Jeelall is supported by an Australian National University Scholarship, and J.Q. Wang is supported by an Australian Postgraduate Award. This work was supported by a Program Grant and Australia Fellowship from the National Health and Medical Research Council (NHMRC; to C.C. Goodnow), Australian government funding of the Australian Phenomics Network and the Australian National University, and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (to A. Kallies and S.L. Nutt).