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Publication : Bim-mediated apoptosis is not necessary for thymic negative selection to ubiquitous self-antigens.

First Author  Hu Q Year  2009
Journal  J Immunol Volume  183
Issue  12 Pages  7761-7
PubMed ID  19933852 Mgi Jnum  J:157488
Mgi Id  MGI:4430966 Doi  10.4049/jimmunol.0902181
Citation  Hu Q, et al. (2009) Bim-mediated apoptosis is not necessary for thymic negative selection to ubiquitous self-antigens. J Immunol 183(12):7761-7
abstractText  T cell education in the thymus is critical for establishing a functional, yet self-tolerant, T cell repertoire. Negative selection is a key process in enforcing self-tolerance. There are many questions that surround the mechanism of negative selection, but it is currently held that apoptosis initiated by Bim and/or Nur77 is critical for negative selection. Recent studies, however, have questioned the necessity of Bim in maintaining both central and peripheral T cell tolerance. To reconcile these apparently contradictory findings, we examined the role of Bim in negative selection in the well-characterized, physiological HY(cd4) mouse model. We found that while Bim expression was required for CD4(+)CD8(+) double-positive thymocyte apoptosis, it was not required for negative selection. Furthermore, Bim deficiency did not alter the frequency or affinity of male reactive cells that escape negative selection in an oligoclonal repertoire. Collectively, these studies indicate that negative selection occurs efficiently in the absence of apoptosis and suggest that the current paradigm of negative selection requiring apoptosis be revisited.
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