T cell up-regulation of B cells via their idiotypes contributing to the development of systemic lupus erythematosus. A hypothesis.
A mechanism for sustained production of pathogenic autoantibody subsets in patients and mice with systemic lupus erythematosus may be centered on selective up-regulation of B cells bearing certain idiotypes. Public idiotypes are characteristic of some autoantibodies, including anti-DNA. Evidence is reviewed that suggests that immunoglobulins bearing certain public idiotypes, such as IdGN2, contain autoantibody subsets that are nephritogenic in human systemic lupus erythematosus and in New Zealand black/New Zealand white F1 mice. Up-regulation of such cells could promote development of nephritis. Work from several laboratories has shown that production of immunoglobulin G antibodies to DNA depends upon T cell help. In New Zealand black/New Zealand white F1 mice, cloned T cells are dominated by autoreactive cells that produce B cell growth factors. We suggest that this sustained release of B cell growth factors combined with selection by T helper cells for B cells bearing IdGN2 are a major mechanism for sustained up-regulation of nephritogenic subsets of autoantibodies.
Hahn
B H
BH
Department of Medicine, University of California, Los Angeles 90024.
Ando
D
D
Ebling
F M
FM
Panosian-Sahakian
N
N
Tsao
B
B
Kalunian
K C
KC
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D004247:DNA