Activation of human B lymphocytes by 8' substituted guanosine derivatives

The 8-substituted guanosine derivatives (8-sGs), mercaptoguanosine and bromoguanosine, are shown to induce immunoglobulin production and proliferation in a subset of normal human B lymphocytes. Limiting dilution analysis indicated that the 8-sG-responsive B cell pool is approximately 10 times larger than that activated by pokeweed mitogen (PWM), 10 times smaller than that activated by Epstein-Barr virus (EBV), and contains approximately equal proportions of cells committed to the expression of IgG, IgA or IgM isotypes. Although some B cells seem able to respond to 8-sGs in the absence of T helper cells, maximal immunoglobulin production is only observed in the presence of T cells. The 8-sG response pattern of human B lymphocytes appeared similar but not identical to that reported for rodent cells. The mitogenic 8-sGs are unique activators as they bypass surface membrane interactions obligatory for other agents including anti-IgM, Staphylococcus aureus particles, PWM, and EBV.