Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas-mediated apoptosis.
CD40--CD40L interactions between resting B cells and activated T cells are essential for germinal center formation. It has been shown that CD40L can induce both Fas expression and susceptibility to Fas-mediated killing in B cells, while anti-Ig can partially rescue B cells from Fas-mediated killing. However, the intracellular mechanism for this phenomenon is not known. We examined the expression of Fas and bcl-2 family gene products, such as Bcl-2, Bcl-x, Bax, and Mcl-1, in human tonsillar B cells. The activation of naive B cells by CD40L induced transient expression of Bcl-xL. As the Bcl-xL level decreased in CD40-activated B cells, the cells became susceptible to apoptosis by anti-Fas antibodies. Though anti-Ig did not change the Fas expression, it protected CD40-activated B cells from Fas-mediated killing by up-regulating Bcl-xL expression. The addition of anti-Ig did not significantly change Bcl-2, Bax, and Mcl-1 levels compared to those of B cells activated by CD40L alone.
Zhang
X
X
Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
Li
L
L
Choe
J
J
Krajewski
S
S
Reed
J C
JC
Thompson
C
C
Choi
Y S
YS
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2; D015854:Up-Regulation; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology*
C494811:BCL2L1 protein, human; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D023201:CD40 Ligand