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Dryad

Data from: Targeted checkpoint control of B cells undergoing positive selection in germinal centers by follicular regulatory T cells

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Jan 08, 2024 version files 16.05 GB

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Abstract

Follicular regulatory T cells (Tfr) can play opposite roles in the regulation of germinal center (GC) responses. Depending on the studies, Tfr suppress or support GCs and B cell affinity maturation. However, which factors determine positive versus negative effects of Tfr on the GC B cells is unclear. In this study we show that GC centrocytes that express MYC upregulate expression of CCL3 chemokine that is essential for both the positive and negative regulation of GC B cells by Tfr. B cell intrinsic expression of CCL3 contributes to Tfr-dependent positive selection of foreign Ag-specific GC B cells. At the same time, expression of CCL3 is critical for direct Tfr-mediated suppression of GC B cells that acquire cognate to Tfr nuclear proteins. Our study suggests that CCR5 and CCR1 receptors promote Tfr migration to CCL3 and highlights Ccr5 expression on Tfr subset that expresses Il10. Based on our findings and previous studies, we suggest a model of chemotactically-targeted checkpoint control of B cells undergoing positive selection in GCs by Tfr, where Tfr directly probe and license foreign antigen-specific B cells to complete their positive selection in GCs but, at the same time, suppress GC B cells that present self-antigens cognate to Tfr.