| First Author | Dvorscek AR | Year | 2022 |
| Journal | EMBO Rep | Volume | 23 |
| Issue | 9 | Pages | e54677 |
| PubMed ID | 35801309 | Mgi Jnum | J:333521 |
| Mgi Id | MGI:7341318 | Doi | 10.15252/embr.202254677 |
| Citation | Dvorscek AR, et al. (2022) IL-21 has a critical role in establishing germinal centers by amplifying early B cell proliferation. EMBO Rep 23(9):e54677 |
| abstractText | The proliferation and differentiation of antigen-specific B cells, including the generation of germinal centers (GC), are prerequisites for long-lasting, antibody-mediated immune protection. Affinity for antigen determines B cell recruitment, proliferation, differentiation, and competitiveness in the response, largely through determining access to T cell help. However, how T cell-derived signals contribute to these outcomes is incompletely understood. Here, we report how the signature cytokine of follicular helper T cells, IL-21, acts as a key regulator of the initial B cell response by accelerating cell cycle progression and the rate of cycle entry, increasing their contribution to the ensuing GC. This effect occurs over a wide range of initial B cell receptor affinities and correlates with elevated AKT and S6 phosphorylation. Moreover, the resultant increased proliferation can explain the IL-21-mediated promotion of plasma cell differentiation. Collectively, our data establish that IL-21 acts from the outset of a T cell-dependent immune response to increase cell cycle progression and fuel cyclic re-entry of B cells, thereby regulating the initial GC size and early plasma cell output. |
