Large granular lymphocytes (LGL) may exert regulatory influences on B cell immunoglobulin synthesis. We, therefore, investigated the influence of LGL from controls and B cell chronic lymphocytic leukemia patients (B-CLL) on control B cell proliferation to costimulation with the F(ab'), fragment of goat antihuman p and B cell growth factor (BCGF). Purified LGL (>go% by morphology) from control and B-CLL peripheral blood were added in various concentrations to purified control B cells and incubated with anti-p and BCGF for 3 days. [3H]-thymidine uptake of B cells was then measured. There was no proliferation of control or CLL LGL alone to the costimulatory signals of the F(ab'), fragments of goat antihuman p chain and BCGF. Addition of control LGL to equal numbers of control B cells did not blunt control B cell responsiveness to BCGF (with control LGL 8,649+298 cpm vs. control B cells alone 8,336 k 556 cpm, mean k SEM). When control LGL were increased to 1O:l LGL:B cell ratio, the maximal inhibition by control
LGL of control B cell proliferative response to BCGF was 23%. In contrast, addition of CLL LGL at a 1:l LGL:B cell ratio resulted in marked impairment of the control B cell proliferative response to BCGF (with CLL LGL 3,586 k 954 cpm vs. control B cells alone 8,649 f 298 cpm). Inhibition by CLL LGL occurred in a cell-concentration-dependent manner. No difference in CLL LGL's inhibitory effect on either resting or activated control B cell responsiveness to BCGF was noted. Inhibition of de novo protein synthesis (by cycloheximide inhibition) of CLL LGL did impair CLL LGL's inhibitory capacity for BCGFinduced B cell proliferation. A possible explanation for these findings includes the possibility that a subgroup of LGL with B cell suppressive activity may have expanded as a host response to the B cell leukemia or as part of the disordered cell regulation in B-CLL.