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.
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology / Q000473:pathology; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000473:pathology; D004912:Erythrocytes / Q000276:immunology / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology*; D007945:Leukemia, Lymphoid / Q000276:immunology* / Q000378:metabolism; D008297:Male; D012756:Sheep; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D007518:Isoantibodies