Gα13 restricts nutrient driven proliferation in mucosal germinal centers.
Nat Immunol
; 25(9): 1718-1730, 2024 Sep.
Article
de 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes B
/
Souris knockout
/
Centre germinatif
/
Sous-unités alpha G12-G13 des protéines G
/
Prolifération cellulaire
/
Complexe-1 cible mécanistique de la rapamycine
Limites:
Animals
Langue:
En
Journal:
Nat Immunol
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
États-Unis d'Amérique