M. Eray et al., P72(SYK) PROTEIN-TYROSINE KINASE - AN EARLY TRANSDUCER OF SLGG-TRIGGERED APOPTOTIC SIGNALING IN HUMAN FOLLICULAR LYMPHOMA-CELLS, International immunology (Print), 10(10), 1998, pp. 1573-1581
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.