TY - JOUR
T1 - IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation
AU - Petersone, Lina
AU - Wang, Chun Jing
AU - Edner, Natalie M
AU - Fabri, Astrid
AU - Nikou, Spyridoula-Angeliki
AU - Hinze, Claudia
AU - Ross, Ellen M
AU - Ntavli, Elisavet
AU - Elfaki, Yassin
AU - Heuts, Frank
AU - Ovcinnikovs, Vitalijs
AU - Rueda Gonzalez, Andrea
AU - Houghton, Luke P
AU - Li, Hannah M
AU - Zhang, Yang
AU - Toellner, Kai-Michael
AU - Walker, Lucy S K
N1 - © 2023 Petersone et al.
Funding
Funder(s): Wellcome
Award Id(s): 220772/Z/20/Z
Funder(s): Medical Research Council
Award Id(s): MR/N001435/1
Funder(s): Marie Skłodowska-Curie
Award Id(s): No. 955321
PY - 2023/10/2
Y1 - 2023/10/2
N2 - Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), the archetypal follicular helper T cell (Tfh) cytokine, shapes the scale and polarization of spontaneous chronic autoimmune as well as transient immunization-induced GC. We find that IL-21 receptor deficiency results in smaller GC that are profoundly skewed toward a light zone GC B cell phenotype and that IL-21 plays a key role in selection of light zone GC B cells for entry to the dark zone. Light zone skewing has been previously reported in mice lacking the cell cycle regulator cyclin D3. We demonstrate that IL-21 triggers cyclin D3 upregulation in GC B cells, thereby tuning dark zone inertial cell cycling. Lastly, we identify Foxo1 regulation as a link between IL-21 signaling and GC dark zone formation. These findings reveal new biological roles for IL-21 within GC and have implications for autoimmune settings where IL-21 is overproduced.
AB - Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), the archetypal follicular helper T cell (Tfh) cytokine, shapes the scale and polarization of spontaneous chronic autoimmune as well as transient immunization-induced GC. We find that IL-21 receptor deficiency results in smaller GC that are profoundly skewed toward a light zone GC B cell phenotype and that IL-21 plays a key role in selection of light zone GC B cells for entry to the dark zone. Light zone skewing has been previously reported in mice lacking the cell cycle regulator cyclin D3. We demonstrate that IL-21 triggers cyclin D3 upregulation in GC B cells, thereby tuning dark zone inertial cell cycling. Lastly, we identify Foxo1 regulation as a link between IL-21 signaling and GC dark zone formation. These findings reveal new biological roles for IL-21 within GC and have implications for autoimmune settings where IL-21 is overproduced.
U2 - 10.1084/jem.20221653
DO - 10.1084/jem.20221653
M3 - Article
C2 - 37466652
SN - 0022-1007
VL - 220
JO - The Journal of Experimental Medicine
JF - The Journal of Experimental Medicine
IS - 10
M1 - e20221653
ER -