Unmasking of cryptic natural killer (NK) cell recognition sites on chronic lymphocytic leukemia lymphocytes

The sensitivity of chronic lymphocytic leukemia (CLL) lymphocytes to attack by natural killer (NK) cells has remained questionable. To clarify this issue, freshly isolated lymphocytes of 37 patients with B-CLL, five with WDLL and two with HCL, were tested with a standard cytotoxicity assay with NK cells from normal donors. All these targets were resistant to cytolysis by the effectors. Freeze-fracture analysis of CLL cell plasma membranes revealed that they have a larger number of intramembranous particles (IMP) associated with the external leaflet (E-face) than have normal lymphocytes. Unlike other neoplastic cells, exposure of CLL lymphocytes to phorbol esters or treatment with neuraminidase did not render them vulnerable to attack by NK cells, nor did 5 days of culture have an effect. Incubation of CLL lymphocytes with anti-Ig-mu (24-72 hr) or with 0.1% pepsin (15 min) resulted in 15% and 27% cytolysis, respectively. B-lymphocytes from the blood of healthy donors were not killed when treated similarly: These data establish that freshly isolated B-CLL lymphocytes are resistant to NK cytolysis but that in contrast to normal B-cells, they possess cryptic NK-recognition structures, which may be uncovered by surface modulation.