|
|
 Previous Article | Table of Contents | Next Article 
Apoptosis induced by polyclonal antilymphocyte globulins in human B- cell
lines
N Bonnefoy-Berard, L Genestier, M Flacher, JP Rouault, G Lizard, M Mutin and JP Revillard
Laboratory of Immunology INSERM U 80, Lyon, France.
Antilymphocyte and antithymocyte globulins (ALG) are currently used as
immunosuppressive agents in clinical transplantation and for the treatment
of severe aplastic anemia. ALG contain a mixture of antibodies that
recognize T- and B-cell-specific antigens but mostly nonlineage-specific
molecules. We reported previously that ALG could inhibit the proliferation
of activated B cells and B cell lines (Bonnefoy-Berard et al, Blood
79:2164, 1992). We show here that ALG induce apoptosis of several human
hematopoietic cell lines, as shown by nuclear condensation and
fragmentation in fluorescence and electronic microscopy and by
double-strand DNA breaks shown by DNA electrophoresis. Apoptosis was
achieved without elevation of intracellular Ca2+ and requirement for mRNA
and protein synthesis. Most of the B-cell lines tested (Epstein-Barr virus
[EBV]-transformed lymphoblastoid cell lines, EBV-negative and groups I/III
EBV-positive Burkitt's lymphoma cell lines, as well as other B-lymphoma
cell lines) were susceptible to ALG-induced cytotoxicity. Myelomonocytic
and T-cell lines were much less susceptible than B-cell lines.
Susceptibility to ALG-induced cytotoxicity was not correlated with
intracellular Bcl-2 level. Most cell lines that express high levels of
Fas/Apo-1 antigen were susceptible to ALG. However, several lines of
evidence support the conclusion that, in addition to Fas/Apo-1, other cell
surface molecules can mediate ALG-induced apoptosis. The cytotoxic activity
could be fully removed by adsorption on susceptible cell lines but not on a
resistant cell line, indicating that it was mediated by antibodies specific
for surface antigens expressed only on susceptible cell lines. Apoptosis
was triggered by ALG F(ab')2 fragments as well as by intact ALG. This
cytotoxic property of ALG may account for their antiproliferative effect
and might contribute to some extent to the relatively lower risk of
posttransplant lymphoproliferative disorders previously reported in
ALG-treated patients.
Volume 83,
Issue 4,
pp. 1051-1059,
02/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. Ayuk, J. A. Perez-Simon, A. Shimoni, A. Sureda, T. Zabelina, R. Schwerdtfeger, R. Martino, H. G. Sayer, A. Alegre, J.-J. Lahuerta, et al.
Clinical impact of human Jurkat T-cell-line-derived antithymocyte globulin in multiple myeloma patients undergoing allogeneic stem cell transplantation
Haematologica,
September 1, 2008;
93(9):
1343 - 1350.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Zand, T. Vo, T. Pellegrin, R. Felgar, J. L. Liesveld, J. J. Ifthikharuddin, C. N. Abboud, I. Sanz, and J. Huggins
Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin
Blood,
April 1, 2006;
107(7):
2895 - 2903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Genestier, S. Fournel, M. Flacher, O. Assossou, J.-P. Revillard, and N. Bonnefoy-Berard
Induction of Fas (Apo-1, CD95)-Mediated Apoptosis of Activated Lymphocytes by Polyclonal Antithymocyte Globulins
Blood,
April 1, 1998;
91(7):
2360 - 2368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Genestier, R. Paillot, N. Bonnefoy-Berard, G. Meffre, M. Flacher, D. Fevre, Y. J. Liu, P. Le Bouteiller, H. Waldmann, V. H. Engelhard, et al.
Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I alpha 1 Domain
Blood,
November 1, 1997;
90(9):
3629 - 3639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
