Enhanced response of autoantibody-secreting B cells from young [formula omitted] mice to T-cell-derived differentiation signals

Abstract

Spleen cells from young NZB NZW mice spontaneously produce IgM antihistone and anti-DNA antibodies in culture, and this in vitro autoantibody production is T-cell dependent. In the present studies, we investigated the response of young autoantibody-producing NZB NZW B cells to various T-cell-derived signals. Stimulation with unprimed allogeneic T cells resulted in a 10- to 20-fold increase in IgM antihistone and anti-DNA antibody production compared with cultures of B cells alone. The responding cells were found in the large B-cell fraction after separation on Percoll gradients. Allo-stimulated B cells from nonautoimmune mice produced much lower absolute amounts of IgM autoantibodies as well as total IgM compared with NZB NZW cells. Marked IgM antinuclear antibody and total IgM production was also observed when NZB NZW B cells were cultured with supernatants from T H2 but not T H1 T-helper clones. Although B cells from nonautoimmune mice produced high levels of autoantibodies after stimulation with lipopolysaccharide, only minimal levels were secreted in response to the active supernatants. These results suggest that young NZB NZW mice have IgM autoantibody-producing B cells that are more sensitive to certain T-cell-derived signals compared with B cells from normal mice. Although these hyperresponsive NZB NZW cells appear to be in an advanced stage of activation, they require additional T-cell signals to express this abnormality.