Kim Youngjun, Manara Francesca, Grassmann Simon, Belcheva Kalina T, Reyes Kanelly, Kim Hyunu, Downs-Canner Stephanie, Yewdell William T, Sun Joseph C, Chaudhuri Jayanta
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.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell Rep. 2025 Jan 28;44(1):115190. doi: 10.1016/j.celrep.2024.115190. Epub 2025 Jan 9.
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.
T细胞衍生的细胞因子白细胞介素-21（IL-21）对生发中心（GC）反应至关重要，但其在B细胞功能中的精确作用仍不清楚。利用IL-21受体（Il21r）条件性敲除小鼠和体外培养系统，我们证明IL-21对B细胞具有双重作用。虽然IL-21以STAT3依赖的方式诱导幼稚B细胞凋亡，但它促进了预激活B细胞，特别是IgG1 B细胞的强劲增殖。在体内，B细胞特异性Il21r缺失损害免疫后IgG1反应，并破坏从前GC状态到GC状态的进展。虽然Il21r缺陷不影响GC B细胞中IgG1细胞的比例，但它大大降低了浆母细胞/浆细胞群体中IgG1细胞的比例。总体而言，我们的研究结果表明，IL-21作为B细胞命运的关键调节因子，以上下文依赖的方式影响B细胞凋亡和增殖。
