Role of complement and B lymphocytes in Sjögren's syndrome-like autoimmune exocrinopathy of NOD.B10-H2b mice.
Sjögren's syndrome (SjS) is a human autoimmune disease characterized by the loss of exocrine function as a result of a chronic immune attack directed primarily against the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). NOD.B10-H2b mice manifest many features of SjS, exhibiting exocrine gland dysfunction concomitant with leukocyte infiltration of the salivary and lacrimal glands. Recent studies have shown that both SjS patients and NOD.B10-H2b mice exhibit increased B lymphocyte survival, B cell hyper-reactivity and hyper-gammaglobulinemia with high production of autoantibodies. To study the possible influence of complement on the development and expression of SjS-like disease of the NOD.B10-H2b, we have utilized a prophylactic treatment with CVF known to interfere with the action of complement C3 factor. NOD.B10-H2b mice, injected with CVF starting at 10 weeks of age, a time when leukocyte infiltration is expected to begin, failed to develop salivary dysfunction out to 24 weeks of age, a time when reduced salivary flow rates are known to occur in non-treated animals. Concomitant with retention of salivary exocrine function, CVF-treated mice showed reduced levels of leukocytic infiltration, reduction of anti-nuclear autoantibodies and major alterations in the B lymphocyte profiles while maintaining general pathophysiological measures of disease. These data suggest that C3 plays a significant role in development and onset of SjS-like disease, yet additional studies need to be carried out to identify the precise mode of action.
Nguyen
Cuong
C
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, P.O. Box 100275, University of Florida, Gainesville, FL 32610, USA.
Cornelius
Janet
J
Singson
Eric
E
Killedar
Smruti
S
Cha
Seunghee
S
Peck
Ammon B
AB
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003176:Complement C3 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000633:toxicity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D012472:Salivation; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013363:Submandibular Gland / Q000473:pathology
D000974:Antibodies, Antinuclear; D003176:Complement C3; D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins