Fig. 4: Follicular immune responses involving IL-21 leads to downregulation of CD19 in ASC.

a, b Gene Set Enrichment Analysis (GSEA) based on gene signatures from ex vivo-differentiated plasmablasts in presence of different cytokine combinations (data sets from Stephenson et al.³⁵). Briefly, naive B cells were cultured in differentiating conditions for 6 days after which different cytokines were added to the culture. After 12 or 24 h, cells were harvested and sequenced. Gene signatures were identified by comparing the different conditions and time points to 0 h. a Density plots of ASC (time points and vaccine protocols combined) with significant enrichment identified by GSEA of gene signatures from ex vivo-differentiated plasmablasts. b Density plots of BMPC with significant enrichment identified by GSEA of gene signatures from ex vivo-differentiated plasmablasts. Violin plots of the normalised enrichment score (NES) per BMPC cluster are depicted in Supplementary Fig. 6a. Statistical significance between NES scores is shown in Supplementary Data 1 (two-tailed Mann–Whitney U test). c, d T follicular helper cells (Tfh, CD19⁻CD4⁺CD45RA⁻CXCR5⁺⁺) from tonsils or T peripheral helper cells (Tph, CD19⁻CD4⁺CD45RA⁻CXCR5⁻) from BAL of sarcoidosis patients were co-cultured 1:1 with tonsillar memory B cells (CD19⁺CD4⁻IgD⁻CD38⁻) for 7 days in presence of staphylococcal enterotoxin B (SEB). Where indicated, T-cell help was blocked with an anti-CD40L antibody and/or recombinant soluble IL-21R. c Histograms of CD19 expression by differentiated plasmablasts (see Supplementary Fig. 7). Two Tfh and two Tph donors were analysed. d Frequencies of CD19^hi plasmablasts. Statistics were performed using an RM parametric one-way ANOVA followed by multiple testing according to Fischer’s LSD test. Source data are provided as a Source Data file.