RESUMEN
We examine whether B cell lines enriched for DNA specificity from either autoimmune (BWF1) or normal mice (Balb/c) can be rendered unresponsive to autoantigen in terms of the specific suppression of direct antibody-forming cells to DNA. These B cell lines were both Lyt-1 positive and negative. Preincubation with oligonucleotide, covalently linked to mouse gamma-globulin, specifically suppressed the antigen-driven response elicited by DNA horse red blood cells in B cell lines from both strains of mice. There is a 5-fold difference in susceptibility to DNA-specific tolerance induction between B cell lines of BWF1 and Balb/c mice. Thus, B cells from autoimmune mice do not appear to have an inherent absolute defect in being rendered tolerant to autoantigen, but are relatively less susceptible to DNA-specific tolerance than nonautoimmune cell lines.
Asunto(s)
Linfocitos B/inmunología , ADN/inmunología , Tolerancia Inmunológica , Animales , Autoantígenos/administración & dosificación , Autoinmunidad , Línea Celular , RatonesRESUMEN
Generalized increase in immunoglobulin secretion, which is a prominent feature of autoimmune diseases, may be due to abnormal T cell regulation, intrinsic abnormality of B cells, or both. To investigate this question we developed nonmalignant continuous B lymphocyte lines from 20-week-old BWF1 mice and compared their growth and immune response to that of BALB/c mice cell lines. The B cell lines contain less than 1% T cells and macrophages and require growth factors from phytohemagglutinin-stimulated EL-4 lymphoma (GF) or recombinant interleukin 4 for continuous growth. No antigens or mitogens are required for growth. In the presence of 20% GF (which is optimal for BALB/c cell growth and immune function) spontaneous growth of BWF1 B cells, and spontaneous entry into G1, was similar to that of BALB/c B cells. With concentrations of GF and anti-mu which were optimal for BALB/c, the growth and immune response of isolated BWF1 B cells are no different from those of BALB/c controls, but at suboptimal doses of GF there is a significant increase of both spontaneous immunoglobulin secretion and response to anti-mu in BWF1 B cells. Thus, these autoimmune B cells are more sensitive to the effects of both T cell factors and immunoglobulin receptors stimulation.