B lymphocytes are resistant to death receptor 5-induced apoptosis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 139; no. 1; pp. 21 - 31
• Main Authors: Crowder, Roslyn N, Zhao, Hong, Chatham, W. Winn, Zhou, Tong, Carter, Robert H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-04-2011; Elsevier
• Subjects: Adolescent; Adult; Allergy and Immunology; Antibodies, Monoclonal; Apoptosis - physiology; B lymphocyte; B-Lymphocytes - physiology; Biological and medical sciences; Cancer; Death receptor 5; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - physiology; Humans; Lupus Erythematosus, Systemic; Male; Medical sciences; Middle Aged; Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Systemic lupus erythematosus; Young Adult; Death receptor 5; B lymphocyte; Systemic lupus erythematosus; Cancer; Immunopathology; Connective tissue disease; Skin disease; Autoimmune disease; B-Lymphocyte; Malignant tumor; Resistance; Immunology; Cell death; Systemic disease; Apoptosis
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2010.12.006

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.