Self-tolerance is one of the key features of the immune system. It is established by many processes during lymphocyte development and requires that antigen-presenting cells provide the appropriate signals (immunogenic or tolerogenic) to T cells. Defects at any stage can result in autoimmunity, and three articles this month consider immune tolerance and autoimmunity from different angles. On page 762, Andrew Mellor and David Munn discuss recent advances in our understanding of the ability of dendritic cells to upregulate expression of indoleamine 2,3-dioxygenase, an event that promotes tolerance induction. In the Opinion article on page 825, Michael Carroll proposes that the complement system is crucial for the induction of B-cell tolerance and suggests that this explains the protective role of complement in systemic lupus erythematosus. Finally, Yuti Chernajovsky, David Gould and Osvaldo Podhajcer summarize the development of gene therapy approaches to treat autoimmune diseases on page 800.

Another key feature of the immune system is the diversity of the antigen-receptor repertoire. However, the antigen receptors expressed by an individual T or B cell are identical and are generated by gene rearrangement at only one of the antigen-receptor loci. The epigenetic mechanisms by which this allelic exclusion is regulated are described on page 753 by Yehudit Bergman and Howard Cedar.

In addition to antigen-receptor signals, lymphocyte activation is regulated by signals from other cell-surface molecules. On page 775, Gail Bishop discusses the distinct and overlapping functions in B cells of a family of adaptor molecules that transduce tumour-necrosis factor receptor (TNFR) signals, the TNFR-associated factors (TRAFs).