Autoantibody production in Sjögren's syndrome: a hypothesis regarding defects in somatic diversification of germ line encoded genes.
Patients with primary Sjögren's syndrome (SS) have rheumatoid factor (anti-IgG Fc antibody, RF) in their sera that contains a crossreactive idiotype (CRI) defined by monoclonal antibody 17-109. This CRI is shared by SS patients and certain patients with Waldenstrom's macroglobulinemia. This CRI was not found in increased frequency in RF from rheumatoid arthritis patients lacking SS. The structural basis for this CRI is the highly conserved kappa chain of the Vk IIIb sub-subgroup. In SS patients, the CRI is present on both IgA RF and IgM RF, accounting for 5-20% of the total RF. Recent studies have shown that a germ line encoded kappa variable region gene (Humkv 325, cloned from a placental DNA library) has DNA sequence that encodes the variable region amino acid sequences of CRI positive kappa chains. Using MoAb 17-109, we have been able to determine the tissue distribution of CRI+ B-cells. We found an increased frequency in the salivary gland biopsies of SS patients and also in their intestinal mucosal tissues (i.e. Peyer's patch). In comparison, we also detected an increased frequency of CRI+ B-cells in the Peyer's patch regions of normals. Taken together, these results suggest that CRI+ B-cells may play an important role in normal mucosal immunity and these CRI+ B-cells have migrated to the salivary gland in SS patients as part of the inflammatory process directed at autoantigens or exogenous antigen(s) located at a mucosal surface.(ABSTRACT TRUNCATED AT 400 WORDS)
Fox
R I
RI
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, California 92037.
Fong
S
S
Chen
P P
PP
Kipps
T J
TJ
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D014644:Genetic Variation; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D012217:Rheumatoid Factor / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D012217:Rheumatoid Factor