Type I interferon (IFN-alpha/beta) rescues B-lymphocytes from apoptosis via PI3Kdelta/Akt, Rho-A, NFkappaB and Bcl-2/Bcl(XL).
Although IFN-alpha was reported to promote the survival of peripheral B-lymphocytes via the PI3-kinase-Akt pathway, the triggered signalling pathways involved in the protection of B cell from apoptosis need to be clarified. Using flow cytometry and western blot analysis, we have found that type 1 IFNs (IFN-alpha/beta) protect human B cells in culture from spontaneous apoptosis and from apoptosis mediated by anti-CD95 agonist, in a dose- and time-dependant manner. IFN-alpha/beta-mediated anti-apoptotic effect on human B cells was totally abrogated by blockade of IFNR1 chain. Our data indicate that PI3Kdelta, Rho-A, NFkappaB and Bcl-2/Bcl(XL) are active downstream of IFN receptors and are the major effectors of IFN-alpha/beta-rescued B cells from apoptosis. Furthermore, immunohistochemical results show marked reduction in numbers of CD20 positive B cell in both spleen and Peyer's patches from mice treated with anti-IFNR1 blocking antibody compared with control group. Moreover, ultrastructural observations of these organs show an obvious increase in apoptotic cells from mice treated with anti-IFNR1 blocking antibody. Our results provide more details about the triggered signalling pathways and the phosphorylation cascade which are involved in the protection of B cell from apoptosis after treatment with IFN-alpha/beta.
Badr
Gamal
G
Zoology Department, Faculty of Science, Assiut University, Egypt; Zoology Department, Faculty of Science, King Saud University, Saudi Arabia. badr73@yahoo.com
Saad
Heba
H
Waly
Hanan
H
Hassan
Khadega
K
Abdel-Tawab
Hanem
H
Alhazza
Ibrahim M
IM
Ahmed
Emad A
EA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D058534:Class I Phosphatidylinositol 3-Kinases; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007156:Immunologic Memory; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D017471:Receptors, Interferon / Q000276:immunology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D051020:bcl-X Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D000577:Amides; D019138:Antibodies, Blocking; C477872:IC 87114; D007093:Imidazoles; D007370:Interferon Type I; D016328:NF-kappa B; D010455:Peptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D011799:Quinazolines; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C118258:SN50 peptide; D051020:bcl-X Protein; C108830:Y 27632; D058534:Class I Phosphatidylinositol 3-Kinases; C421683:Pik3cd protein, mouse; D051058:Oncogene Protein v-akt; D054460:rho-Associated Kinases; D000225:Adenine; C093642:SB 203580