title: B lymphocytes are resistant to death receptor 5-induced apoptosis.
abstract: Death Receptor 5 (DR5) induces apoptosis in various types of cells and is a potential therapeutic target. We have investigated whether targeting DR5 could be used to eliminate pathogenic B lymphocytes from systemic lupus erythematosus (SLE) patients. We examined DR5 expression and function on B lymphocytes from healthy controls subjects, SLE patients, and human tonsil. DR5 was expressed similarly on all B cell subpopulations, including resting and activated B cells. Expression of DR5 was equivalent on B cells from SLE patients and healthy subjects. Additionally, DR5 expression was unchanged after B lymphocyte stimulation. However, B cells were resistant to DR5-induced apoptosis, including after in vitro activation. No changes in subsets of B cells were observed in subjects of a trial of CS-1008, an agonist anti-DR5. While DR5 shows promise as a way to selectively eliminate tumor cells and activated synoviocytes, these data suggest DR5 alone cannot be used as a target to remove pathogenic SLE B cells.
authors.affiliation: Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Roslyn N
authors.initials: RN
authors.lastname: Crowder
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: W Winn
authors.initials: WW
authors.lastname: Chatham
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carter
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic; D008297:Male; D008875:Middle Aged; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand