Expansion of follicular helper T cells in the absence of Treg cells: implications for loss of B-cell anergy.
The maintenance of B-cell anergy is essential to prevent the production of autoantibodies and autoimmunity. However, B-cell extrinsic mechanisms that regulate B-cell anergy remain poorly understood. We previously demonstrated that regulatory T (Treg) cells are necessary for the maintenance of B-cell anergy. We now show that in Treg-cell-deficient mice, helper T cells are necessary and sufficient for loss of B-cell tolerance/anergy. In addition, we show that the absence of Treg cells is associated with an increase in the proportion of CD4(+)  cells that express GL7 and correlated with an increase in germinal center follicular helper T (GC-T(FH) ) cells. These GC-T(FH)  cells, but not those from Treg-cell-sufficient hosts, were sufficient to drive antibody production by anergic B cells. We propose that a function of Treg cells is to prevent the expansion of T(FH)  cells, especially GC-T(FH)  cells, which support autoantibody production.
Division of Allergy/Immunology, Department of Pediatrics, Medical College of Wisconsin, The Children's Research Institute, Milwaukee, WI 53226, USA.
Steven M
SM
Leonardo
Jessica L
JL
De Santis
Ashley
A
Gehrand
Laurent P
LP
Malherbe
Stephen B
SB
Gauld
D000818:Animals; D000917:Antibody Formation; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy; D018858:Germinal Center / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000943:Antigens, Differentiation; D001323:Autoantibodies; C096712:antigen GL7