Large granular lymphocytes from B‐chronic lymphocytic leukemia patients inhibit normal B cell proliferation

Large granular lymphocytes (LGL) may exert regulatory influences on B cell immuno‐globulin 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′)₂ fragment of goat antihuman μ and B cell growth factor (BCGF). Purified LGL (>90% by morphology) from control and B‐CLL peripheral blood were added in various concentrations to purified control B cells and incubated with anti‐μ, 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′)₂ fragments of goat antihuman μ 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 ± 556 cpm, mean ± SEM). When control LGL were increased to 10:1 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 1:1 LGL:B cell ratio resulted in marked impairment of the control B cell proliferative response to BCGF (with CLL LGL 3,586 ± 954 cpm vs. control B cells alone 8,649 ± 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 BCGF‐induced 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.