P72(SYK) PROTEIN-TYROSINE KINASE - AN EARLY TRANSDUCER OF SLGG-TRIGGERED APOPTOTIC SIGNALING IN HUMAN FOLLICULAR LYMPHOMA-CELLS

Cross-linking of B cell antigen receptor (sIg) elicits different biolo gical responses, including cell activation, proliferation, differentia tion, anergy and cell death depending on the maturational stage of the cell. We established the tumor cell lines HF-1.3.4 and HF-4-9 from tw o patients with follicular lymphoma. Both cell lines carry the charact eristic t(14;18) chromosomal translocation and display constitutively overexpressed Bcl-2, HF-1.3.4 represents a mature B cell with sIgG and several somatic hypermutations in its Ig genes, while HF-4-9 is a les s mature B cell, expressing sIgM and only a few mutations in its Ig ge nes. Cross-linking of sig with antibodies leads to apoptosis in HF-1.3 .4 cells but not in HF-4-9 cells. Triggering of sIg induced, within se conds, identical tyrosine phosphorylation of p53/56(lyn) protein tyros ine kinase (PTK) and p55(blk) PTK in both of the cell lines; however, a prominent tyrosine phosphorylation and activation of p72(syk) PTK on ly in HF-1.3.4 cells. We conclude that p72(syk) PTK is of importance i n relaying apoptotic signalling upon sig crosslinking in the HF-1.3.4 cell line. Given the mature phenotype of the HF-1.3.4 cell line it ser ves as a model for the late negative selection during B cell ontogeny. Moreover, our results question the current concept that a constitutiv e overexpression of Bcl-2 confers resistance to sig ligation-induced a poptosis in lymphoma cells.