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 follicular lymphoma (FL) patient, and HF-4 and HF-9 from another. All cell lines carry the characteristic t(14;18) chromosomal translocation 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 calcium signal in all three lines but only HF-1 is induced to apoptosis. Treatment with anti-Ig arrests the proliferation of HF-1 within 6-12 h, nucleosomal DNA fragmentation is evident in 18 h and 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 expression of bcl-2 per se renders resistance to apoptosis but that the balance between the expression of bcl-2 and c-myc may dictate the outcome of sIg cross-linking. HF-1 is a unique, phenotypically mature human 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 anti-cancer treatment based on anti-sIg antibody induced apoptosis.
Eray
M
M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Tuomikoski
T
T
Wu
H
H
Nordström
T
T
Andersson
L C
LC
Knuutila
S
S
Kaartinen
M
M
D017209:Apoptosis / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004587:Electrophoresis, Agar Gel; D016259:Genes, myc; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007074:Immunoglobulin G; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium