Autoimmunity and Glomerulonephritis After Neonatal Induction of Lymphoid Chimerism in Mice: Role of Donor B Cells and Host T Cells

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 playa dominant role in the pathogenesis of this autoimmune diseasesince 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 immuno globulins arepresent in the kidney eluate of chimenc mice. In vitro experimentsindicate that I cells from diseased Balb/c mice induce activationof F₁ donor B cells with secretion of anti-DNA antibodies. Thesefindings suggest that a host-versus-graft reaction between recipientT cells and donor F₁ B cells is responsible for the secretionof pathogenic antibodies in this model.