title: Involvement of NFAT1 in B cell self-tolerance.
abstract: B cells from anti-lysozyme Ig/soluble lysozyme double-transgenic mice are chronically exposed to self-Ag in the periphery, resulting in an anergic phenotype. Chronic exposure to self-Ag leads to nuclear translocation of NFAT1 and NFAT2, suggesting that they are involved in anergy. To directly test a role for NFAT1 in B cell anergy, NFAT1-deficient mice were crossed with anti-lysozyme Ig transgenic mice. As expected, B cell anergy was evident in the presence of self-Ag based on reduced serum anti-lysozyme levels, percentage and number of mature B cells, and reduced B cell responsiveness. By contrast, B cell anergy was relieved in NFAT1(-/-) mice expressing soluble self-Ag. Bone marrow development was equivalent in NFAT1-sufficient and -deficient mice, suggesting that loss of anergy in the latter is due to selection later in development. Taken together, these studies provide direct evidence that the transcription factor NFAT1 is involved in B cell anergy.
authors.affiliation: CBR Institute for Biomedical Research, Harvard University, Boston, MA 02115, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Barrington
authors.forename: Madhuri
authors.initials: M
authors.lastname: Borde
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011828:Radiation Chimera; D017634:Self Tolerance / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse