IL-21 shapes the B cell response in a context-dependent manner
Youngjun Kim,
Francesca Manara,
Simon Grassmann,
Kalina T. Belcheva,
Kanelly Reyes,
Hyunu Kim,
Stephanie Downs-Canner,
William T. Yewdell,
Joseph C. Sun,
Jayanta Chaudhuri
Affiliations
Youngjun Kim
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Corresponding author
Francesca Manara
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Simon Grassmann
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Kalina T. Belcheva
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA
Kanelly Reyes
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Hyunu Kim
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USA
Stephanie Downs-Canner
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
William T. Yewdell
Department of Immunology Discovery, Genentech Inc, South San Francisco, CA 94080, USA
Joseph C. Sun
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USA
Jayanta Chaudhuri
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USA; Corresponding author
Summary: The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1+ B cells. In vivo, B-cell-specific Il21r deletion impaired IgG1 responses post-immunization and disrupted progression from pre-GC to GC states. Although Il21r deficiency did not affect the proportion of IgG1+ cells among GC B cells, it greatly diminished the proportion of IgG1+ cells among the plasmablast/plasma cell population. Collectively, our findings suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner.
