In vitro beta2-microglobulin (β2m) secretion by normal and leukaemic B-cells: effects of recombinant cytokines and evidence for a differential response to the combined stimulus of phorbol ester and calcium ionophore

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Abstract
Due to the increasing therapeutic use of immunoregulatory agents and the potential effects on cellular function, we examined the modulation of in vitro beta2-microglobulin (.beta.2m) production rates by ''normal'' tonsil and leukaemic B-cells in response to a number of these agents. Tonsil B-cells responded to phorbol ester (TPA) by an increased .beta.2m production rate, which was further enhanced by the combined stimuli of TPA plus the calcium ionophore A23187. In marked contrast, however, lymphocytes from a majority (8/11) of B-cell malignancies showed a suppression of the TPA-induced .beta.2m production rate in response to the combined TPA/A23187 stimulus. These different responses of ''normal'' and malignant B-cells were not apparent when IgM production rates were examined. The recombinant cytokines IL-1, IL-2, IFN-.alpha., IFN-.gamma. and TNF also enhanced .beta.2m production rates of both normal and leukaemic B-cells, but to a considerably lesser extent than did TPA. Bryostatin-1 increased .beta.2m production to a level intermediate between that obtained by TPA and the cytokines. It is suggested that .beta.2m production rates may correspond to the degree of B-cell differentiation, and/or to the degree of cellular ''activation''. The results further indicate that the in vitro measurement of .beta.2m production provides a different index of the cellular response than that obtained by the conventional measurement of IgM production.