A dual role for both CD40-ligand and TNF-alpha in controlling human B cell death.
Members of the TNF-R family are instrumental in controlling lymphoid cell death and survival. A major role in the regulation of murine and human B cell survival and differentiation has been attributed to CD40/CD40-ligand (CD40-L) interactions, but recent in vitro and in vivo data implicate that other receptor-ligand pairs might also be involved. We have used the human Burkitt lymphoma cell line Ramos as a model system to identify additional TNF-R/TNF family members that are implicated in the regulation of B cell apoptosis. Ligation of B cell receptor (BCR) with anti-IgM mAb for 48 h induced apoptosis in approximately 68% of the Ramos B cells. Interestingly, not only CD40 mAb but also rTNF-alpha could efficiently inhibit BCR-induced B cell death. In addition, activated T cells also prevented BCR-triggered apoptosis, and this effect was inhibited completely by a combination of blocking Abs against CD40-L and TNF-alpha. In contrast to the strong effect of BCR ligation, APO-1 mAb induced apoptosis in only +/- 18% of the Ramos cells after 48 h. Noticeably, addition of CD40 mAb or rTNF-alpha increased the percentage of cells (+/- 46%) undergoing apoptosis, which correlated with an increase of Fas/APO-1 membrane expression induced by CD40 or TNF-R ligation. Taken together, we show that CD40/CD40-L and TNF-R/TNF-alpha interactions not only postpone or prevent B cell death, but are also involved in sensitizing B cells for Fas-ligand (Fas-L)-dependent death.
Lens
S M
SM
Department of Clinical (Viro-)Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
Tesselaar
K
K
den Drijver
B F
BF
van Oers
M H
MH
van Lier
R A
RA
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology*; D023201:CD40 Ligand; D017637:Clonal Deletion / Q000502:physiology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000145:classification / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D011947:Receptors, Antigen, B-Cell; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C044203:anti-IgM; D019014:fas Receptor; D023201:CD40 Ligand