Work

IL-21 shapes the B cell response in a context-dependent manner

Year: 2025

Type: article

Abstract: 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. • IL-21 induces apoptosis in naive B cells but promotes proliferation in activated B cells • IL-21 promotes preferential expansion of IgG1 + B cells through synergy with BCR signaling • Il21r deletion in B cells leads to quantitative and qualitative defects in GC responses Kim et al. observed that IL-21 regulates B cell fate in a context-dependent manner. IL-21 induces apoptosis in naive B cells but promotes proliferation of activated B cells, especially IgG1 + cells. B-cell-specific IL-21 receptor deficiency impairs GC formation and IgG1 antibody production.

Source: Cell Reports

DOI: 10.1016/j.celrep.2024.115190