The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells

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 C...

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Vydané v:Immunity (Cambridge, Mass.) Ročník 41; číslo 6; s. 1026
Hlavní autori: Sage, Peter T, Paterson, Alison M, Lovitch, Scott B, Sharpe, Arlene H
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 18.12.2014
Predmet:
Animals
Antibody Formation
B-Lymphocytes - immunology
B7-1 Antigen - genetics
B7-1 Antigen - metabolism
B7-2 Antigen - genetics
B7-2 Antigen - metabolism
Cell Differentiation
Cells, Cultured
CTLA-4 Antigen - genetics
CTLA-4 Antigen - metabolism
Down-Regulation
Germinal Center - immunology
Immune Tolerance
Mice
Mice, Inbred Strains
Mice, Knockout
Mice, Transgenic
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Regulatory - immunology
ISSN:1097-4180, 1097-4180
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Popis
Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2014.12.005