In vitro induction of IgG anti‐DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR‐restricted T cell clone

SUMMARY An HLA‐DR restricted T cell clone (26G11) which recognized a lymphoid cell‐derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4 + B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti‐DNA antibody production in DR‐matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR‐matched normal control subjects produced large amounts of IgM anti‐DNA antibody, but did not produce IgG anti‐DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR‐matched patients with active SLE spontaneously produced a fairly large amount of IgG anti‐DNA antibody, and the production was augumented by the T cell clone. Little IgG anti‐DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD‐B) and high density B (HD‐B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti‐DNA antibody was spontaneously produced by LD‐B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti‐DNA antibody was not spontaneously produced by the HD‐B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti‐DNA antibody‐producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production.