¹The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Correspondence: Professor A Strasser, Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. E-mail: strasser@wehi.edu.au

²Current address: La Trobe University, Bundoora, Australia.

Received 12 October 2007; Accepted 13 October 2007; Published online 20 November 2007.

Abstract

Tolerance to self-antigens within the adaptive immune system is safeguarded, at least in part, through deletion of autoreactive T and B lymphocytes. This deletion can occur during the development of these cells in primary lymphoid organs, the thymus or bone marrow, respectively, or at the mature stage in peripheral lymphoid tissues. Deletion of autoreactive lymphocytes is achieved to a large extent through apoptotic cell death. This review describes current understanding of the mechanisms that mediate apoptosis of autoreactive lymphocytes during their development in primary lymphoid organs and during their activation in the periphery. In particular, we discuss the roles of the proapoptotic Bcl-2 family member Bim and the small family of Nur77-related transcriptional regulators in lymphocyte negative selection. Finally, we speculate on the processes that may lead to the activation of Bim when antigen receptors are activated on autoreactive T or B cells.