Clonal Deletion

John H Russell, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri, USA

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

Clonal deletion refers to the process of eliminating unwanted clones of cells by death of the progenitors. At different points in development, the process eliminates lymphocyte (B and T cell) progenitors either through the stimulation or failure to stimulate their clonally unique, membrane-bound antigen receptors. Clonal deletion is an important, general mechanism to limit the development and expansion of autoreactive lymphocyte populations that would cause autoimmune disease (Figure 1). Clonal deletion may also play an important role in limiting the organism's response to tumors.

Our early understanding of the interaction between pathogens and lymphocytes relied on the 'selective' expansion of appropriate lymphocyte clones in response to antigenic challenge. This allowed the maintenance of a pool of precursor lymphocytes to a broad range of pathogens that could be expanded through proliferation of the most appropriate clones for a specific pathogenic challenge. The lymphocyte clones with the highest affinity for pathogenic antigens would be selected for expansion because their receptor stimulation was the most effective. The paradoxical notions that antigen receptor stimulation could lead to nonresponsiveness through death (clonal deletion) or anergy as well as expansion of the progenitor has changed our fundamental understanding of lymphocyte biology. The antigen receptor can no longer be modeled as a digital on/off switch. Rather, the context in which the antigen is presented as well as the differentiation/activation state of the responding lymphocyte determines the lymphocyte's functional response.

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