Human T-bet governs the generation of a distinct subset of CD11c high CD21 low B cells - Archive ouverte HAL
Article Dans Une Revue Science Immunology Année : 2022

Human T-bet governs the generation of a distinct subset of CD11c high CD21 low B cells

Rui Yang
Danielle Avery
Katherine Jackson
Masato Ogishi
Ibtihal Benhsaien
Likun Du
Xiaofei Ye
Jing Han
Jérémie Rosain
Imagine - Institut des maladies génétiques (IHU)
Jessica Peel
  • Fonction : Auteur
Marie-Alexandra Alyanakian
  • Fonction : Auteur
Bénédicte Neven
  • Fonction : Auteur
Sarah Winter
Imagine - Institut des maladies génétiques (IHU)
Anne Puel
Imagine - Institut des maladies génétiques (IHU)
Bertrand Boisson
Imagine - Institut des maladies génétiques (IHU)
Kathryn Payne
Melanie Wong
  • Fonction : Auteur
Amanda Russell
Yoko Mizoguchi
  • Fonction : Auteur
Satoshi Okada
Gulbu Uzel
  • Fonction : Auteur
Christopher Goodnow
Sylvain Latour
Imagine - Institut des maladies génétiques (IHU)
Jalila El Bakkouri
Aziz Bousfiha
Kahn Preece
Paul Gray
  • Fonction : Auteur
Baerbel Keller
Klaus Warnatz
Stéphanie Boisson-Dupuis
Imagine - Institut des maladies génétiques (IHU)
Laurent Abel
Imagine - Institut des maladies génétiques (IHU)
Qiang Pan-Hammarström
Jacinta Bustamante
Imagine - Institut des maladies génétiques (IHU)
Cindy Ma
Jean-Laurent Casanova
Imagine - Institut des maladies génétiques (IHU)
Stuart Tangye

Résumé

High-level expression of the transcription factor T-bet characterizes a phenotypically distinct murine B cell population known as “age-associated B cells” (ABCs). T-bet–deficient mice have reduced ABCs and impaired humoral immunity. We describe a patient with inherited T-bet deficiency and largely normal humoral immunity including intact somatic hypermutation, affinity maturation and memory B cell formation in vivo, and B cell differentiation into Ig-producing plasmablasts in vitro. Nevertheless, the patient exhibited skewed class switching to IgG1, IgG4, and IgE, along with reduced IgG2, both in vivo and in vitro. Moreover, T-bet was required for the in vivo and in vitro development of a distinct subset of human B cells characterized by reduced expression of CD21 and the concomitantly high expression of CD19, CD20, CD11c, FCRL5, and T-bet, a phenotype that shares many features with murine ABCs. Mechanistically, human T-bet governed CD21 lo CD11c hi B cell differentiation by controlling the chromatin accessibility of lineage-defining genes in these cells: FAS , IL21R , SEC61B , DUSP4 , DAPP1 , SOX5 , CD79B , and CXCR4 . Thus, human T-bet is largely redundant for long-lived protective humoral immunity but is essential for the development of a distinct subset of human CD11c hi CD21 lo B cells.

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Sciences du Vivant [q-bio]

Sylvain LATOUR  : Connectez-vous pour contacter le contributeur

https://hal.science/hal-03864150

Soumis le : lundi 21 novembre 2022-16:38:00

Dernière modification le : jeudi 11 avril 2024-11:20:14

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Rui Yang, Danielle Avery, Katherine Jackson, Masato Ogishi, Ibtihal Benhsaien, et al.. Human T-bet governs the generation of a distinct subset of CD11c high CD21 low B cells. Science Immunology, 2022, 7 (73), ⟨10.1126/sciimmunol.abq3277⟩. ⟨hal-03864150⟩

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