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
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.