Clonal Deletion

T lymphocytes are massively produced in the thymus and, once generated, will not rearrange their receptors. Memory T cells are very long lived, and there is no clear evidence that new ones are generated after the thymus ceases to function in early adulthood. Therefore, elimination of autoreactive T cells must occur at the production site (thymus) at the time the cells are differentiating their T-cell receptor (TCR) repertoire. Once a T-cell clone has been eliminated, there is no risk of reemergence of that particular clone.

B-cell clonal deletion involves different mechanisms than T-cell clonal deletion. B cells are continuously produced by bone marrow throughout life, and they initially express low-affinity immunoglobulin (Ig) M on their membranes. In most instances, interaction of these resting B cells with circulating self-molecules neither activates them nor causes their elimination. Selection and deletion of autoreactive clones seem to take place in the peripheral lymphoid organs during onset of the immune response. At that time, activated B cells can modify the structure of their membrane immuno-globulin as a consequence of somatic mutations in their germline genes. B cells expressing self-reactive immunoglobulins of high affinity can emerge from this process, and their elimination takes place in the germinal centers of the peripheral lymphoid tissues (Blackman et al. 1990, von Boehmer 1994, Cyster et al. 1994).

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