IMMUNOGLOBULIN VARIABLE-REGION STRUCTURES IN IMMUNITY AND AUTOIMMUNITY TO DNA

Citation
Tn. Marion et al., IMMUNOGLOBULIN VARIABLE-REGION STRUCTURES IN IMMUNITY AND AUTOIMMUNITY TO DNA, Tohoku Journal of Experimental Medicine, 173(1), 1994, pp. 43-63
Citations number
65
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
00408727
Volume
173
Issue
1
Year of publication
1994
Pages
43 - 63
Database
ISI
SICI code
0040-8727(1994)173:1<43:IVSIIA>2.0.ZU;2-J
Abstract
Important to the immunopathology associated with the autoimmune diseas e systemic lupus erythematosus, is the production of autoantibody to D NA. Crucial to understanding the immunological basis for autoimmunity to DNA is knowing whether the anti-DNA autoantibody is the product of clonally-selective, antigen-specific B cell stimulation or non-selecti ve, polyclonal B cell activation. Structural analyses of the immunoglo bulin variable-regions of both early, IgM and late, IgG anti-DNA antib odies from lupus-prone (NZB x NZW) F-1 mice have indicated that both I gM and IgG anti-DNA autoantibodies are generated by clonally-selective B cell stimulation. Within individual autoimmune mice the later appea ring, IgG anti-DNA autoantibodies are structurally similar to the earl ier appearing, IgM antibodies, and in some cases both IgM and IgG may be produced by the same B cell clones. The variable-region structural data also suggest that DNA or complexes containing DNA may be the immu nogenic stimuli for autoantibody to DNA. In support of this conclusion , normal mice immunized with immunogenic peptide-DNA complexes produce anti-DNA antibodies with structural and serological characteristics s imilar if not identical to those of autoimmune anti-DNA antibodies. No rmal mice immunized with peptide-DNA complexes eventually develop immu nopathology that resembles lupus nephritis. These results suggest that autoimmunity to DNA and subsequent autoimmune disease in SLE may resu lt from a specific immune response to DNA containing antigens.