CD6 LIGATION MODULATES THE BCL-2 BAX RATIO AND PROTECTS CHRONIC LYMPHOCYTIC-LEUKEMIA B-CELLS FROM APOPTOSIS INDUCED BY ANTI-IGM/

CD6 and CD5 belong to a scavenger-receptor cysteine-rich (SRCR) super family of membrane glycoproteins that are expressed on chronic lymphoc ytic leukemia B (B-CLL) cells, normal T cells, and a small subset of n ormal B cells, CD6 configures in the membrane in relation to the cellu lar activation level and can act as a coreceptor for T-cell activation , We have examined a group of progressive and nonprogressive B-CLL cel ls. Most B-CLL cells were positive for CD6 and the expression of CD6 w as increased after activation with Staphylococcus aureus Cowan I plus interleukin-2 or 12-O-tetradecanoylphorbol 13-acetate, although anti-C D6 antibodies did not increase proliferative responses to these stimul i, However, anti-CD6 stimulation was found to protect against anti-IgM -induced apoptosis in B-CLL, bar, upregulation and bcl-2 downregulatio n were found in anti-IgM- and glucocorticoid (GCC)-induced apoptotic c ells, respectively, Furthermore, CD6 cross-linking downregulated bar, mRNA levels in anti-IgM-treated cells, resulting in an increased bcl-2 /bax(alpha) ratio, CD6 activation also prevented bcl-2 mRNA downregula tion and apoptosis induced by GCC in one of six GCC-sensitive patients , These data suggest that an interaction between CD6 and its ligand mi ght contribute to B-CLL survival through the modulation of the Bcl-2/B ax ratio, (C) 1997 by The American Society of Hematology.