BLyS and BLyS receptor expression in non-Hodgkin's lymphoma.

Abstract

B Lymphocyte Stimulator (BLyS) protein and its receptor are new members of the tumor necrosis factor family, with specific effects exclusively on B cells. We have studied the tumor cell expression of the BLyS-Receptor (BLyS-R) and the serum BLyS protein levels in patients with different types of non-Hodgkin's lymphomas (NHL). BLyS-R expression was assessed by flow cytometry on B cells from 43 NHL patients and 10 normal donors. BLyS protein serum levels were analyzed by ELISA. All B cells, tumor and normal, expressed BLyS-R. The mean fluorescence intensity (MFI +/- SD) of BLyS-R on normal B cells was 25.2 +/- 2.3 arbitrary units, while follicular NHL and chronic lymphocytic leukemia (CLL) exhibited significantly lower expression of the BLyS-R (17.7 +/- 3.1; 15.5 +/- 3.9, respectively, p < 0.0001 for both); other lymphoma subtypes expressed levels comparable to normal B cells (diffuse large cell, 24.8 +/- 4.3; mantle cell, 20 +/- 4.7; marginal zone, 20.7 +/- 3.7). BLyS protein serum levels were analyzed in 15 normal donors and 17 patients with follicular NHL. Levels of BLyS protein were, on average, threefold higher in patients with follicular lymphoma compared to normal donors (mean +/- SD; 13.4 +/- 5.6 ng/mL vs 4.6 +/- 0.7 ng/mL; p < 0.0001). BLyS protein alone was unable to stimulate proliferation in cultures of follicular lymphoma B cells or normal B cells. The specificity of the expression of BLyS-R by B-cell lymphomas opens new opportunities for the treatment of these cancers by targeting this ligand-receptor pair.