CROSS-LINKING OF SURFACE IGG INDUCES APOPTOSIS IN A BCL-2 EXPRESSING HUMAN FOLLICULAR LYMPHOMA LINE OF MATURE B-CELL PHENOTYPE

We have established three lymphoma cell lines, HF-1 from one follicula r lymphoma (FL) patient, and HF-4 and HF-9 from another, All cell line s carry the characteristic t(14;18) chromosomal translocation and expr ess constitutively the bcl-2 gene product (Bcl-2 protein), Cross-linki ng of their surface membrane Igs (slgs) with relevant antibodies trigg ers a vigorous calcium signal in all three lines but only HF-1 is indu ced to apoptosis, Treatment with anti-lg arrests the proliferation of HF-1 within 6-12 h, nucleosomal DNA fragmentation is evident in 18 h a nd a morphologically complete apoptosis is seen in 24-48 h. While bcl- 2 was expressed at equal levels in all lines, the apoptosis-sensitive HF-1 line displayed a much lower expression of c-myc than seen in the apoptosis-resistant line, This finding challenges the concept that exp ression of bcl-2 per se renders resistance to apoptosis but that the b alance between the expressions of bcl-2 and c-myc may dictate the outc ome of sig cross-linking, HF-1 is a unique, phenotypically mature huma n B cell line expressing surface IgG, This cell line offers a new tool for investigations on apoptosis and induction of tolerance in mature B lymphocytes. Our results suggest that some FLs may be amenable to an ti-cancer treatment based on anti-slg antibody induced apoptosis.