Studies on the in vitro behavior of agammaglobulinemic lymphocytes.

Circulating lymphocytes from patients with congenital X-linked agammaglobulinemia, sporadic congenital agammaglobulinemia, and acquired agammaglobulinemia have been cultured in vitro. They have been shown to proliferate in a normal manner under stimulus of phytohemagglutinin and antigens to which the patient was sensitized. Agammaglobulinemic cells have been shown to synthesize protein at a rate similar to that of normal cells, and the character of the extracellular protein produced is also similar. Agammaglobulinemic lymphocytes have been found to produce a small quantity of immunoglobulin G, similar to that found in normal cell cultures. The quantity of immunoglobulin produced may be increased by exposure of the cells to phytohemagglutinin. From these data, it appears that the basic lesion responsible for agammaglobulinemia is not a deficiency in lymphocyte-mediated antigen recognition or cellular proliferation. It would also appear that the basic deficiency in these disorders does not involve the structural or regulatory genes necessary for the synthesis of immunoglobulins. By exclusion, the pathogenesis of the deficiency would appear to involve cells other than circulating lymphocytes.