Maternal Ig mediates neonatal tolerance in rheumatoid factor transgenic mice but tolerance breaks down in adult mice.
We have recently demonstrated that B cell deletion occurs in the bone marrow of IgHa high affinity anti-IgG2a(a) (RF) transgenic mice. Here we demonstrate via genetic crosses that the source of IgG2a is the mother, thus establishing a transplacental mechanism that ensures tolerance to developmentally expressed Ags. Since maternal IgG can mediate tolerance in young mice, whether tolerance is maintained or, instead, autoimmunity ensues after weaning was investigated. We find that deletion remits abruptly in these RF transgenic mice beginning at 2 to 3 wk postweaning, and some degree of autoreactivity can be observed thereafter for weeks to months. The mechanism of sustained expression of autoreactive RF B cells in normal mice is unclear as yet, but a plausible mechanism is that once self-reactive cells are present, the antibody they secrete markedly reduces the autoantigen levels, presumably allowing further development, rather than deletion, of newly arising B lineage cells. The phenotype of these RF transgenic mice suggests a positive feedback mechanism that tends to perpetuate autoimmunity once it has been established. If such a mechanism were to exist in autoimmune animals, it could have important implications for the establishment and maintenance of B and T cell tolerance in chronic autoimmune diseases.
Wang
H
H
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Shlomchik
M J
MJ
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017637:Clonal Deletion / Q000235:genetics; D005260:Female; D007108:Immune Tolerance / Q000235:genetics*; D007112:Immunity, Maternally-Acquired / Q000235:genetics*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D014886:Weaning
D007074:Immunoglobulin G; D012217:Rheumatoid Factor