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From the * Institut National de la Santé et de la Recherche Médicale U 291, F-34197 Montpellier,
France; Interleukin-4 (IL-4) provides support for humoral immune responses through upregulation of
T helper (Th) type 2 cell differentiation, but it is not known whether IL-4 promotes antibodymediated autoimmune diseases such as systemic lupus erythematosus (SLE). Here, we show
that the constitutive expression of an IL-4 transgene by B cells completely prevents the development of lethal lupus-like glomerulonephritis in the (NZW × C57BL/6.Yaa)F1 murine
model of SLE. This was associated with marked changes in the serum levels of IgG subclasses,
rather than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrease of IgG2a,
and an increase in IgG1 subclasses, and by a strong reduction in the serum levels of gp70-antigp70 immune complexes. This effect of the transgene appears to result from a modulation of
the Th1 versus Th2 autoimmune response, since the protected mice displayed comparably
modified IgG2a and IgG3 antibody response against exogenous T cell-dependent antigen, but
not against T cell-independent antigens. Thus, IL-4 prevents the development of this lupuslike autoimmune disease, most likely by downregulating the appearance of Th1-mediated IgG subclasses of autoantibodies such as the IgG3 autoantibodies which have been shown to be especially nephritogenic.
Department of Pathology, Medical Center of the University of Geneva, CH-1211 Geneva 4, Switzerland; and § Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
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