Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren's syndrome.
The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjögren's syndrome. NOD.Igmu null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from parental NOD mice or human primary Sjögren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren's syndrome.
Robinson
C P
CP
Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA.
Brayer
J
J
Yamachika
S
S
Esch
T R
TR
Peck
A B
AB
Stewart
C A
CA
Peen
E
E
Jonsson
R
R
Humphreys-Beher
M G
MG
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology; D005088:Exocrine Glands / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018727:Muscarinic Antagonists / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000276:immunology / Q000378:metabolism; D012463:Saliva / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000503:physiopathology
D001323:Autoantibodies; D007074:Immunoglobulin G; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate