Malignant chronic lymphocytic leukemia B cells express interleukin 2 receptors but fail to respond to interleukin 2's proliferative signal

The functional importance of interleukin 2 (IL-2) receptors in the regulation of malignant B cell proliferation still remains to be clarified. We studied malignant CLL B cells for the presence of IL-2 receptors and responsiveness to IL-2 with respect to proliferation and B cell colony formation. Seven of 25 B-cLL patients studied had reactivity for anti-Tac (mean, 11.8%; range 4-31%). Purified control T cells expressed less than 2% reactivity to anti-Tac. CLL B cell colony forming cells were reactive with anti-Tac in all five patients studied (mean, 24.8%; range, 17-31%). The proliferative response of control and CLL B cells to both a partially purified preparation of IL-2 and recombinant Il-2 (rIL-2) was also examined. Control B cells demonstrated a dose-dependent, enhanced proliferative response to IL-2. At lower IL-2 concentrations (2-200 units/ml), rIL-2 appeared to have a more significant proliferative enhancing effect on control B cells than did the partially purified Il-2 preparation. In contrast, no concentration of the IL-2 preparations enhanced CLL B cells' proliferative response. The monoclonal antibody anti-Tac was capable of inhibiting control B cell responsiveness to IL-2. rIL-2 did not support CLL B cell colony formation. Thus, malignant B cell populations may spontaneously express the Tac antigen in the absence of a functional response to IL-2. The significance of this in the treatment of lymphomas is underscored by the development of new therapeutic strategies which would seek to incorporate the use of immunoregulatory lymphokines such as IL-2.