Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 209, Issue 11, Pages 1907-1917Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20112744
Keywords
-
Categories
Funding
- Australian National University Scholarship
- Australian Postgraduate Award
- Program Grant and Australia Fellowship from the National Health and Medical Research Council (NHMRC)
- Australian government funding of the Australian Phenomics Network
- Australian National University
- Victorian State Government Operational Infrastructure Support
- Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme
Ask authors/readers for more resources
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 antigenbinding 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available