The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses.
J Exp Med
; 216(9): 2170-2183, 2019 09 02.
Article
em En
| MEDLINE
| ID: mdl-31311822
ABSTRACT
The E3 ubiquitin ligase Itch regulates antibody levels and prevents autoimmune disease in humans and mice, yet how Itch regulates B cell fate or function is unknown. We now show that Itch directly limits B cell activity. While Itch-deficient mice displayed normal numbers of preimmune B cell populations, they showed elevated numbers of antigen-experienced B cells. Mixed bone marrow chimeras revealed that Itch acts within B cells to limit naive and, to a greater extent, germinal center (GC) B cell numbers. B cells lacking Itch exhibited increased proliferation, glycolytic capacity, and mTORC1 activation. Moreover, stimulation of these cells in vivo by WT T cells resulted in elevated numbers of GC B cells, PCs, and serum IgG. These results support a novel role for Itch in limiting B cell metabolism and proliferation to suppress antigen-driven B cell responses.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Ubiquitina-Proteína Ligases
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Antígenos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article