Impaired mitogen responses of the non-leukaemic B cells from patients with chronic lymphocytic leukaemia.

We investigated the immunological mechanism of the low level of circulating immunoglobulin and depressed primary and secondary responses of patients with chronic lymphocytic leukaemia (B-CLL) using purified non-leukaemic B cells in vitro. To assess the function of the non-leukaemic B cells we separated them from the much larger leukaemic population, which expresses the pan-T cell marker CD5, by immunoabsorption using anti-CD5 antibodies and Dynabeads. Immunoglobulin production was measured after the cells had been cultured with the B cell mitogens, pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain 1 (SAC). Autologous T cells that were found to function normally in our systems were added to cultures containing PWM. Non-leukaemic B cells from 15 B-CLL patients produced 539 ng/ml, immunoglobulin (mean value) with SAC and 162 ng/ml with PWM compared with 14,182 and 5513 ng/ml, respectively, from B cells from normal, age-matched control patients. Most of the immunoglobulin produced in the non-leukaemic B cell cultures carried the light chain associated with the leukaemic clone. We conclude that even at early stages in the disease (12 patients were Rai stage 0 patients) when the total serum immunoglobulin levels are still near normal, the B cells respond poorly to B cell mitogens.