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 onefollicular lymphoma (FL) patient, and HF-4 and HF-9 from another.All cell lines carry the characteristic t(14;18) chromosomaltranslocation and express constitutively the bcl-2 gene product(Bcl-2 protein). Cross-linking of their surface membrane Igs(sigs) with relevant antibodies triggers a vigorous calciumsignal in all three lines but only HF-1 is induced to apoptosis.Treatment with anti-Ig arrests the proliferation of HF-1 within6—:12 h, nucleosomal DNA fragmentation is evident in 18h and a morphologically complete apoptosis is seen in 24–48h. While bcl-2 was expressed at equal levels in all lines, theapoptosis-sensitive HF-1 line displayed a much lower expressionof c-myc than seen in the apoptosis-resistant line. This findingchallenges the concept that expression of bcl-2 per se rendersresistance to apoptosis but that the balance between the expressionsof bcl-2 and c-myc may dictate the outcome of sig cross-linking.HF-1 is a unique, phenotypically mature human B cell line expressingsurface IgG. This cell line offers a new tool for investigationson apoptosis and induction of tolerance in mature B lymphocytes.Our results suggest that some FLs may be amenable to anti-cancertreatment based on anti-slg antibody induced apoptosis.