Figure 2: a) Experimental model used to investigate the impact of IL-21 produced by non-cognate T cells on GC B cells. The IL-21 produced by adoptively transferred OVA-specific OTII T cells was sensed by non cognate B1-8hi NP-specific B cells. b) The availability of IL-21 in the local microenvironment influences the fate of GC B cells, with higher levels leading to increased proliferation, and plasma cell formation.
Quast and colleagues showed that IL-21 acts locally on T and B cells, independently of direct cell-to-cell interaction. The concentration of IL-21 in the microenvironment, both before the establishment of the GC and during the GC reaction, determines the trajectory and dynamics of the immune response. Greater IL-21 availability enhances the early expansion of Tfh cells in the GC, which directly impacts the size of the GC and amplifies the B cell response, leading to the formation of plasma cells.
1. Victora GD, Nussenzweig MC. Germinal Centers. Annu Rev Immunol . Apr 26 2022;40:413-442. doi:10.1146/annurev-immunol-120419-022408
2. Spolski R, Leonard WJ. Interleukin-21: a double-edged sword with therapeutic potential. Nat Rev Drug Discov . May 2014;13(5):379-95. doi:10.1038/nrd4296
3. Quast I, Dvorscek AR, Pattaroni C, et al. Interleukin-21, acting beyond the immunological synapse, independently controls T follicular helper and germinal center B cells. Immunity . Aug 9 2022;55(8):1414-1430 e5. doi:10.1016/j.immuni.2022.06.020
4. Linterman MA, Beaton L, Yu D, et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med . Feb 15 2010;207(2):353-63. doi:10.1084/jem.20091738
5. Zotos D, Coquet JM, Zhang Y, et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med . Feb 15 2010;207(2):365-78. doi:10.1084/jem.20091777
6. Zotos D, Quast I, Li-Wai-Suen CSN, et al. The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21. Nat Commun . Dec 9 2021;12(1):7160. doi:10.1038/s41467-021-27477-0