Polyclonal B cell activation by the Eta-1 cytokine and the development of systemic autoimmune disease.
Studies of systemic autoimmune disease have led to the view that initiation and progression of the disease process reflects chronic and sustained B cell activation by unidentified polyclonal activating agents. In earlier studies, we found that T cells from MRL/1 mice, which develop murine lupus, express very high levels of a newly defined T cell cytokine, Eta-1. Inasmuch as chronic and sustained B cell stimulation by T cells is a cardinal feature of MRL/1 disease, we determined the effects of this cytokine on Ig production by B cells. We show that both recombinant and biochemically purified natural Eta-1 stimulate IgM and IgG production by mixtures of B cells and macrophages from the autoimmune MRL/l strain. Additional studies suggest that optimal Ig production by Eta-1 may require macrophages and reflect enhanced Ig production by large B cells. These findings support the view that elevated levels of endogenous Eta-1 may cause chronic and sustained polyclonal B cell activation that leads to autoimmune disease in this murine model.
Department of Pathology, Harvard Medical School, Boston, MA.
M A
MA
Lampe
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Patarca
M V
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Iregui
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Cantor
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D053495:Osteopontin; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin