Central tolerance is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self. The concept of central tolerance was proposed in 1959 as part of a general theory of immunity and tolerance. It was hypothesized that it is the age of the lymphocyte that defines whether an antigen that is encountered will induce tolerance, with immature lymphocytes being tolerance sensitive. The theory that self-tolerance is 'learned' during lymphocyte development was a major conceptual contribution to immunology. It was experimentally substantiated in the late 1980's when tools to analyze lymphocyte development became available. Central tolerance is distinct from periphery tolerance in that it occurs while cells are still present in the primary lymphoid organs (thymus and bone-marrow), prior to export into the periphery. Peripheral tolerance is generated after the cells reach the periphery. Regulatory T cells can be considered both central tolerance and peripheral tolerance mechanisms, as they can be generated from self (or foreign)-reactive T cells in the thymus during T cell differentiation. However, they exert their immune suppression in the periphery on other self (or foreign)-reactive T cells.
Clonal selection occurs after immature lymphocytes express antigen receptors. The cells with useful receptors are preserved, and many potentially harmful, self antigen-reactive cells are eliminated by processes of selection induced by antigen receptor engagement . The preservation of useful specificities is called positive selection. Positive selection ensures maturation of T cells whose receptors bind weakly to self major histocompatibility complex molecules. Negative selection is the process that eliminates developing lymphocytes whose antigen receptors bind strongly to self antigens present in the lymphoid organs. Both developing B cells and T cells are subject to negative selection during a short period after antigen receptors are expressed. Negative selection of developing lymphocytes is an important mechanism for maintaining central tolerance.
Clonal Selection
clonal selection of the B and T lymphocytes:1. Hematopoietic stem cell 2. Immature lymphocytes with various receptors 3. "Self"-antigens from the body's own tissues 4. Mature, inactive lymphocytes 5. Foreign antigen 6. Cloned activated lymphocytes.