IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation.
Lina PetersoneChun Jing WangNatalie Mona EdnerAstrid FabriSpyridoula-Angeliki NikouClaudia HinzeEllen M RossElisavet NtavliYassin ElfakiFrank HeutsVitalijs OvcinnikovsAndrea Rueda GonzalezLuke P HoughtonHannah M LiYang ZhangKai-Michael ToellnerLucy Sarah Kate WalkerPublished in: The Journal of experimental medicine (2023)
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.
Keyphrases
- cell cycle
- cell proliferation
- gas chromatography
- multiple sclerosis
- stem cells
- signaling pathway
- transcription factor
- poor prognosis
- single cell
- oxidative stress
- adipose tissue
- type diabetes
- metabolic syndrome
- immune response
- dendritic cells
- blood brain barrier
- long non coding rna
- replacement therapy
- skeletal muscle
- insulin resistance
- high fat diet induced
- diabetic rats
- genome wide
- tandem mass spectrometry