Enhanced response of autoantibody-secreting B cells from young NZB/NZW mice to T-cell-derived differentiation signals.
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 TH2 but not TH1 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.
Herron
L R
LR
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado.
Coffman
R L
RL
Kotzin
B L
BL
D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002469:Cell Separation; D007075:Immunoglobulin M / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008222:Lymphokines