Autoimmunity and glomerulonephritis after neonatal induction of lymphoid chimerism in mice: role of donor B cells and host T cells

Abstract

Balb/c mice neonatally injected with semiallogeneic (A/J x Balb/c) F1 or (C57 BL/6 x Balb/c) F1 hybrid spleen cells develop autoantibodies, marked increase in serum levels of IgG1 and IgE, lymphoid hyperplasia, and immune-complex glomerulonephritis. F1 donor B cells play a dominant role in the pathogenesis of this autoimmune disease since B-cell chimerism is required for the occurrence of immunopathology, donor-specific allotype is expressed on serum anti-DNA antibodies, and substantial amounts of donor-derived immunoglobulins are present in the kidney eluate of chimeric mice. In vitro experiments indicate that T cells from diseased Balb/c mice induce activation of F1 donor B cells with secretion of anti-DNA antibodies. These findings suggest that a host-versus-graft reaction between recipient T cells and donor F1 B cells is responsible for the secretion of pathogenic antibodies in this model.