In vitro interaction with antigen suppresses the differentiation of chronic lymphocytic leukemia cells secreting monoclonal anti-sheep red blood cell antibody

Leukemic B cells from a patient with chronic lymphocytic leukemia had membrane-bound IgM that reacted against a sheep red blood cell (SRBC) antigen. A small proportion of these cells was able to differentiate into anti-SRBC hemolytic plaque-forming cells when cultured in vitro in the absence of polyclonal stimulators. The addition of pokeweed mitogen or of X-irradiated allogeneic T cells further enhanced their differentiation. The addition of antigen (SRBC) to unstimulated cultures of the patient's mononuclear cells suppressed the anti-SRBC antibody production. Marked suppression was induced by concentrations of SRBC that were found to stimulate anti-SRBC antibody production optimally by normal peripheral blood mononuclear cells. Two lines of evidence suggest this inhibition was not due to the activation of suppressor cells. First, depletion of T cells with the phenotype reported to be associated with suppressor cells, namely OKT8+ cells, did not prevent suppression. Secondly, the patient's mononuclear cells pulsed with SRBC did not suppress anti-SRBC antibody production by untreated autologous cells in co-culture. These findings suggest that leukemic cells were inhibited by the direct interaction with antigen. This suppression might be the result of intrinsic abnormalities of leukemic B cells. Alternatively, it could be the reflection of a tolerogenic response to antigen stimulation displayed by the patient's leukemic cells, which have a surface phenotype, IgM+D-, that is comparable to that of immature normal B cells.