IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells.
Sci Immunol
; 8(80): eadd1823, 2023 02 24.
Article
in En
| MEDLINE
| ID: mdl-36800413
ABSTRACT
Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (TFH)-derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to induce c-MYC and p-S6 in GCBCs. However, IL-21R plus CD40 stimulation differentially affects GCBC fate compared with BCR plus CD40 ligation-engaging unique molecular mechanisms-as revealed by bulk RNA sequencing (RNA-seq), single-cell RNA-seq, and flow cytometry of GCBCs in vitro and in vivo. Whereas both signal pairs induced BLIMP1 in some GCBCs, only the IL-21R/CD40 combination induced IRF4hi/CD138+ cells, indicative of plasma cell differentiation, along with CCR6+/CD38+ memory B cell precursors. These findings reveal a second positive selection pathway in GCBCs, document rewired IL-21R signaling in GCBCs, and link specific TFH- and Ag-derived signals to GCBC differentiation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Germinal Center
/
Receptors, Interleukin-21
Language:
En
Journal:
Sci Immunol
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos