Browsing by Author "Wu, Shuxian"

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    IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells
    (American Association for the Advancement of Science, 2023) Luo, Wei; Conter, Laura; Elsner, Rebecca A.; Smita, Shuchi; Weisel, Florian; Callahan, Derrick; Wu, Shuxian; Chikina, Maria; Shlomchik, Mark; Microbiology and Immunology, School of Medicine
    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.