MECHANISMS OF TOLERANCE TO SELF

Several mechanisms exist to prevent lymphocytes from reacting against self-antigens. As T cells develop in the thymus and express antigen-sp ecific receptors, those with high-affinity to self-antigens existing w ithin the thymus are deleted. Low-affinity self-reactive T cells and T cells with receptors against antigens not represented intrathymically will mature and join the peripheral T cell pool. They may either igno re self-antigens expressed by tissues unable to activate T cells throu gh a lack of the appropriate costimulator signals,,or they may, under certain conditions, be deleted or rendered anergic and unable to respo nd. Likewise, B cells that express surface Ig receptors with high bind ing affinity to membrane-bound self-antigens present in the bone marro w will be rescued by receptor editing or will be deleted, whereas thos e of lower affinity will migrate to the periphery in either an anergic or indifferent state depending on the degree of receptor engagement b y antigen. Once there, their ultimate fate is determined by the availa bility of T cell help.