Gα13 restricts nutrient driven proliferation in mucosal germinal centers.
Nat Immunol
; 25(9): 1718-1730, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39025963
ABSTRACT
Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Camundongos Knockout
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Centro Germinativo
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Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP
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Proliferação de Células
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Alvo Mecanístico do Complexo 1 de Rapamicina
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
/
Nat. immunol
/
Nature immunology
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos