The literature concerning the atypical lymphocyte is reviewed and an analysis is made of the occurrence, morphology and deoxyribonucleic acid (DNA) synthesis of these cells in normal persons and in patients with a variety of disorders. The atypical lymphocyte is a normal constituent of the human peripheral blood. In normal man 12 per cent or less (mean 7.5 per cent) of the mononuclear cells are atypical lymphocytes. In what is defined as probable atypical lymphocytosis 13 to 19 per cent of the mononuclear cells are atypical lymphocytes. Atypical lymphocytosis is definite when 20 per cent or more of the mononuclear cells are atypical lymphocytes. To evaluate lymphocyte morphology properly fingertip capillary blood is preferred, or as an alternate, freshly smeared anticoagulated blood. Approximately 2 per cent of the atypical lymphocytes are found to be in the phase of DNA synthesis of the cell cycle during an hour's in vitro incubation of normal blood. The increased number of atypical lymphocytes in many nonviral as well as viral illnesses is viewed as a nonspecific cellular response to a stimulus that is probably antigenic. The atypical lymphocyte is analogous in many respects to the "transformed" lymphocyte produced in cell culture by phytohemagglutinin or specific antigen. In many of the atypical lymphocytoses the nature of the antigen is plain: virus, drug hypersensitivity and possibly graft versus host reaction. The burst of DNA synthesis in atypical lymphocytes found early in the course of many conditions associated with atypical lymphocytes probably reflects the rapid production and early release of relatively immature cells of this series. The fate of these cells is not known but they probably are removed from the circulation without reaching mitosis.
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