The thymocytotoxic activity of human sera against guinea pig cells was earlier shown to be mediated by IgM and a heat-labile serum factor, presumably complement. It is not known if such natural cytotoxic activity represents background activity of preexisting clones of immunoglobulin-producing cells, cross-reacting antibodies appearing after immunization, physiological immune regulatory molecules, or components of an immune network. We have therefore examined the presence of thymocytotoxic IgM molecules in normal adult and neonatal sera and in a number of diseases which affect the lymphoid and immune system. The thymocytotoxic effect of serum was measured in different dilutions, both directly and after heat inactivation of the sera and supplementation with a standard amount of IgM-depleted serum, which is inactive in itself but provides a fixed amount of the heat-labile cofactor. The cytotoxic IgM was present in various amounts in all sera tested, although in neonates very small amounts were found. No specific aberration in toxic activity was seen in rheumatoid arthritis or a number of hematological diseases. In general, the cytotoxic activity correlated well with the total amount of IgM. However, in cases of chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura and immunocytoma aberrant cytotoxic activities were found, but to ascertain a connection between these diseases and the factor would require a more extensive follow-up study. The results indicate that the naturally occurring thymocytotoxic IgM is widespread and may reflect a clone of B cells which is activated by an endogenous stimulus, or by some ubiquitous exogenous immunogen.
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