p72(syk) protein tyrosine kinase: An early transducer of slgG-triggered apoptotic signalling in human follicular lymphoma cells

Abstract

Cross-linking of B cell antigen receptor (slg) elicits different biological responses, including cell activation, proliferation, differentiation, 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 two patients with follicular lymphoma. Both cell lines carry the characteristic t(14;18) chromosomal translocation and display constitutively overexpressed Bcl-2 HF-1.3.4 represents a mature a cell with slgG and several somatic hypermutations in its Ig genes, while HF-4-9 is a less mature B cell, expressing slgM and only a few mutations in its Ig genes. Cross-linking of slg with antibodies leads to apoptosis in HF-1.3.4 cells but not in HF-4-9 cells. Triggering of slg induced, within seconds, identical tyrosine phosphorylation of p53/56(lyn) protein tyrosine kinase (PTK) and p55(blk) PTK in both of the cell lines; however, a prominent tyrosine phosphorylation and activation of p72(syk) PTK only in HF-1.3.4 cells. We conclude that p72(syk) PTK is of importance in relaying apoptotic slgnalling upon slg crosslinking in the HF-1.3.4 cell line. Given the mature phenotype of the HF-1.3.4 cell line it serves as a model for the late negative selection during B cell ontogeny. Moreover, our results question the current concept that a constitutive overexpression of Bcl-2 confers resistance to slg ligation-induced apoptosis in lymphoma cells.