Evidence for thymic regulation of autoimmunity in BXSB mice: acceleration of disease by neonatal thymectomy.
BXSB mice spontaneously develop an autoimmune syndrome characterized by autoantibody production, immune complex renal disease, and lymphadenopathy containing B cells. The male BSXB mouse has a rapid onset of disease that is determined by defective stem cells. Although the B cell hyperactivity has been traced to the stem cell, previous studies did not evaluate the T cells of BXSB mice with regard to a role in modifying their natural history. The present study was carried out in an attempt to determine whether or not thymic regulation played a role in modulating the stem-B cell abnormalities in BXSB mice. It was found that neonatal thymectomy led to a marked increase in autoantibody production (anti-RBC, anti-DNA), a dramatic increase in lymphadenopathy, and worsening of renal disease. Flow cytometric analysis of the lymph node cells from intact and thymectomized mice demonstrated a loss of Lyt-2+ cells from the thymectomized mice and an increased proportion of Ly-1+, Thy-1.2- cells. These results indicate that although the B cell hyperactivity of BXSB mice is determined by a marrow stem cell defect, thymic regulation normally serves to dampen that B cell hyperactivity; neonatal thymectomy reduces the thymic regulation of autoimmunity in the BXSB males and leads to excessive B cell numbers and function.
D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D008206:Lymphatic Diseases / Q000209:etiology; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains / Q000276:immunology*; D010641:Phenotype; D011507:Proteinuria / Q000209:etiology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D004247:DNA