Estimation of B-cells transformed by Epstein-Barr virus in patients with congenital agammaglobulinemia.

In vitro immunoglobulin synthesis was measured in lymphocytes from four patients with congenital agammaglobulinemia (cA gamma) stimulated by two different polyclonal B-cell activators, pokeweed mitogen (PWM) and Epstein-Barr virus (EBV). In PWM-stimulated cultures, patient T-cells treated with mitomycin C (MMC) were able to help the immunoglobulin (Ig) synthesis of normal B-cells. Patient B-cell-enriched fraction not containing surface Ig positive cells did not produce Ig in combination with MMC-treated autologous or allogeneic T-cells. Patient lymphocytes were infected with EBV and the subsequent production of Ig was measured. In lymphocytes from control subjects, exponential growth of the cells having EBV-associated nuclear antigen (EBNA) was shown to be associated with an exponential increase in Ig secretion within 1 week after EBV infection. However, in lymphocytes from three of the four patients, it took 2, 4 and 10 weeks, respectively, until lymphocyte-transformation and subsequent Ig-secretion were observed. Lymphocytes from one patient were not transformed nor did they secrete Ig after EBV infection. These results may imply that a small number of B-cells are present in peripheral blood of most of patients with cA gamma, and that they are able to produce the Ig after transformation by EBV which takes a much longer time than in controls.