title: Tolerance induction to self-MHC antigens in fetal and neonatal mouse B cells.
abstract: We have studied the mechanisms of tolerance induction to self-MHC antigens in mouse B cells during fetal development and the post-natal period. To monitor the fate of autoreactive B cell clones, we used the 3-83 micro delta B cell receptor (BCR)-transgenic (Tg) and -knock-in (KI) mouse models. These BCR-Tg and -KI B cells recognize the MHC class I molecules H-2K(k) and H-2K(b), with a high or moderate affinity, respectively. We compared the fate of BCR-Tg and -KI B cells in H-2K(b)-bearing animals and H-2K(b)-negative controls at various stages of their fetal development and post-natal life. Our data show that, in contrast to what occurs in adult B cells, anergy is the main component of tolerance induction in 3-83 micro delta BCR-Tg K(b+) autoreactive fetuses, while 3-83 BCR-KI fetuses primarily use receptor editing. Interestingly, autoreactive B cell deletion is absent or merely marginal before birth. Our results indicate that tolerance induction is effective as early as embryonic day 16.5 and that in the fetus and neonate, like in the adult, the main mechanism of B cell tolerance functioning in the 3-83 KI system is receptor editing. In contrast, in the 3-83 micro delta mice where receptor editing is hindered, adult and fetal B cells differ in their preferential use of mechanisms leading to self-tolerance (i.e. deletion versus anergy).
authors.affiliation: Laboratory of Immune Regulations and Development, Department of Developmental Biology, J. Monod Institute, UMR 7592 (CNRS and Universities Paris 6 and 7), 2 place Jussieu, 75251 Paris cedex 05, France. kanellopoulos@ijm.jussieu.fr
authors.forename: Stéphane M
authors.initials: SM
authors.lastname: Caucheteux
authors.forename: Cécile
authors.initials: C
authors.lastname: Vernochet
authors.forename: Josiane
authors.initials: J
authors.lastname: Wantyghem
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gendron
authors.forename: Colette
authors.initials: C
authors.lastname: Kanellopoulos-Langevin
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D005260:Female; D047109:Fetal Development / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism
chemical_list: D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D011947:Receptors, Antigen, B-Cell