Mechanisms of T and B cell collaboration in the in vitro production of anti-DNA antibodies in the NZB/NZW F1 murine SLE model.
B/W mice spontaneously develop IgG antibodies to DNA that cause lethal immune nephritis. T and B cell interactions in the in vitro anti-DNA antibody response of B/W mice were investigated, and two distinct families of helper T cells that drive these responses were defined. First, the anti-DNA antibody-forming cell (AFC) response was found to be increased in B/W mice with nephritis and was inhibited with the monoclonal antibody anti-L3T4, suggesting a major role for helper T cells. Purified splenic T cells from mice with nephritis were able to augment both the IgG and the IgM anti-DNA AFC response of young B/W B cells. T helper cells were cloned from spleens of NZB/W F female mice with high titer anti-DNA antibodies and nephritis. The cloned T cells augmented both IgG and IgM anti-DNA AFC responses of young B/W B cells. Four clones--27.9, 30.7, 30.8, and 30.10--were selected for further study. These cells proliferated, in the context of syngeneic (H2d/z) antigen-presenting cells (APC) but not to allogeneic APC. Analysis of the mechanism of T helper cell clone-mediated augmentation of anti-DNA AFC revealed two populations: "cognate" T helper cells, which specifically augment anti-DNA AFC (30.7 and 30.10), and non-antigen-specific T helper cells (27.9 and 30.8), which augment the response of B cells of differing specificity by a bystander mechanism, probably through increased release of B cell growth and differentiation factors.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal / Q000276:immunology; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006824:Hybridization, Genetic; D015847:Interleukin-4; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008814:Mice, Inbred NZB / Q000235:genetics / Q000276:immunology*; D008815:Mice, Inbred Strains / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology* / Q000378:metabolism
D000974:Antibodies, Antinuclear; D006133:Growth Substances; D008222:Lymphokines; D015847:Interleukin-4; D004247:DNA