@article {542016, title = {The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells.}, journal = {Immunity}, volume = {41}, number = {6}, year = {2014}, month = {2014 Dec 18}, pages = {1026-39}, abstract = {The receptor CTLA-4 has been implicated in controlling B cell responses, but the mechanisms by which CTLA-4 regulates antibody production are not known. Here we showed deletion of CTLA-4 in adult mice increased Tfh and Tfr cell numbers and augmented B cell responses. In the effector phase, loss of CTLA-4 on Tfh cells resulted in heightened B cell responses, whereas loss of CTLA-4 on Tfr cells resulted in defective suppression of antigen-specific antibody responses. We also found that non-Tfr Treg cells could suppress B cell responses through CTLA-4 and that Treg and/or Tfr cells might downregulate B7-2 on B cells outside germinal centers as a means of suppression. Within the germinal center, however, Tfr cells potently suppress B cells through CTLA-4, but with a mechanism independent of altering B7-1 or B7-2. Thus, we identify multifaceted regulatory roles for CTLA-4 in Tfh, Tfr, and Treg cells, which together control humoral immunity.}, keywords = {Animals, Antibody Formation, Antigens, CD80, Antigens, CD86, B-Lymphocytes, Cell Differentiation, Cells, Cultured, CTLA-4 Antigen, Down-Regulation, Germinal Center, Immune Tolerance, Mice, Mice, Inbred Strains, Mice, Knockout, Mice, Transgenic, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory}, issn = {1097-4180}, doi = {10.1016/j.immuni.2014.12.005}, author = {Sage, Peter T and Paterson, Alison M and Lovitch, Scott B and Sharpe, Arlene H} }