Phorbol ester-induced production of beta-2-microglobulin in B-CLL cells: relation to IgM secretory response and disease activity.

Earlier studies have indicated that serum beta 2m levels correlate with the disease activity, estimated tumour cell mass and prognosis of CLL. We have therefore analysed the spontaneous and phorbol ester (TPA)-induced capacity of CLL cells to produce beta 2m in vitro in relation to disease activity. Cell cultures (greater than 90% B cells) from 15 patients with active disease contained significantly higher (P less than 0.001) levels of beta 2m (0.22 +/- 0.09 mg/l) than cultures from 17 patients with inactive CLL (0.08 +/- 0.06). When TPA-induced CLL cell cultures were compared, this difference was even more striking (0.48 +/- 0.18 versus 0.13 +/- 0.09). The capacity of TPA-treated B-CLL cells to export beta 2m was positively correlated with their capacity to secrete monoclonal IgM (r = 0.73; P less than 0.001). Cell depletion experiments showed that the beta 2m export by B-CLL cells is enhanced by accessory T cells. Four individual CLL patients were followed for 14 months and repeatedly investigated for signs and symptoms of active disease, and the CLL cells were tested for in vitro production of beta 2m. Fluctuations in the clinical activity of the leukaemia were paralleled by similar switches in CLL cell production of beta 2m.