Natural antibodies and pathological states

Recent studies have shown that there are extensive similarities between natural antibodies and the 'pathogenic' antibodies found in various immuno-pathological situations. Thus, in human and murine lupus, a substantial number of the autoantibodies against DNA which can be eluted from renal biopsies are able to react with many other antigens. Polyreac-tive IgM and IgG autoantibodies increase during the development of the murine lupus syndrome and form glomerular immune deposits. Furthermore, monoclonal polyreactive antibodies against DNA derived from lupus mice when injected into normal mice are able to induce nephritis. Many antibodies against DNA are encoded by nonmutated or minimally mutated genes but some show clear evidence of somatic mutations. These results suggest that in lupus, high-affinity mutated 'pathogenic' DNA autoantibodies may arise from germ-line encoded low affinity autoantibodies through an antigen-driven selection. However, germ-line encoded polyreactive natural antibodies without mutations may be pathogenic under certain circumstances.

Similar results were obtained and conclusions reached by analyzing the rheumatoid factor antibodies appearing in rheumatoid arthritis.

Recent studies have shown that antibodies produced after infections are often polyreactive and encoded by nonmutated germ-line genes. Thus, for example, analysis of the expressed V genes for IgG antibodies against herpes simplex virus and varicella-zoster virus showed that these antibodies use the same germ-line VM genes used by autoantibodies. Similarly murine monoclonal antibodies reacting with group A streptococcal antigen were found to react with various autoantigens and to be encoded by unmutated germ-line genes. Furthermore, monoclonal antibodies obtained from Trypanosoma cruzi-infected mice reacting with this parasite were found to be encoded by the germ line and recognized antigens present on the membrane of activated T cells. It would appear, therefore, that infection by viruses, bacteria and parasites stimulates the natural antibody-producing cells, resulting in an increased synthesis of these antibodies.

See also: Affinity; Autoimmune diseases; Autoimmunity; CDS; Gammaglobulin; Idiotype network; Monoclonal antibodies (mAbs); Specificity.

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