The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells.
Autoreactive B cells that appear to be inactivated can be found in healthy individuals. In this study, we examined the potential of these anergic cells to become activated. We show that anergy of anti-double-stranded DNA (dsDNA) B cells in BALB/c mice is readily reversed, requiring only the provision of T cell help. We further show that spontaneous loss of anergy among anti-dsDNA B cells in autoimmune lpr/lpr mice occurs in two phases: an abortive initial response to T help followed by full loss of tolerance. Strikingly, the abortive response can be reproduced in nonautoimmune mice when CD4+CD25+ T regulatory cells are administered in conjunction with CD4+ T helper cells, suggesting that loss of B cell tolerance may require both the production of T cell help and the overcoming of T suppression.
Seo
Su-jean
SJ
The Wistar Institute, Philadelphia, PA 19104, USA.
Fields
Michele L
ML
Buckler
Jodi L
JL
Reed
Amy J
AJ
Mandik-Nayak
Laura
L
Nish
Simone A
SA
Noelle
Randolph J
RJ
Turka
Laurence A
LA
Finkelman
Fred D
FD
Caton
Andrew J
AJ
Erikson
Jan
J
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D017635:Clonal Anergy / Q000276:immunology; D004247:DNA / Q000276:immunology*; D005260:Female; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D018448:Models, Immunological; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C513179:CXCR5 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand; D000069594:Abatacept; D004247:DNA