AUTHOR=Douna Hidde , de Mol J. , Amersfoort Jacob , Schaftenaar Frank H. , Kiss Mate G. , Suur Bianca E. , Kroner Mara J. , Binder Christoph J. , Bot Ilze , Van Puijvelde Gijs H. M. , Kuiper Johan , Foks Amanda C. 

TITLE=IFNγ-Stimulated B Cells Inhibit T Follicular Helper Cells and Protect Against Atherosclerosis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.781436

DOI=10.3389/fcvm.2022.781436

ISSN=2297-055X

ABSTRACT=<p>B and T cells are interconnected in the T follicular helper—germinal center B cell (T<sub>FH</sub>-GC B cell) axis, which is hyperactive during atherosclerosis development and loss of control along this axis results in exacerbated atherosclerosis. Inhibition of the T<sub>FH</sub>–GC B cell axis can be achieved by providing negative co-stimulation to T<sub>FH</sub> cells through the PD-1/PD-L1 pathway. Therefore, we investigated a novel therapeutic strategy using PD-L1-expressing B cells to inhibit atherosclerosis. We found that IFNγ-stimulated B cells significantly enhanced PD-L1 expression and limited T<sub>FH</sub> cell development. To determine whether IFNγ-B cells can reduce collar-induced atherosclerosis, <italic>apoE</italic><sup>−/−</sup> mice fed a Western-type diet were treated with PBS, B cells or IFNγ-B cells for a total of 5 weeks following collar placement. IFNγ-B cells significantly increased PD-L1<sup>hi</sup> GC B cells and reduced plasmablasts. Interestingly, IFNγ-B cells–treated mice show increased atheroprotective Tregs and T cell-derived IL-10. In line with these findings, we observed a significant reduction in total lesion volume in carotid arteries of IFNγ-B cells-treated mice compared to PBS-treated mice and a similar trend was observed compared to B cell-treated mice. In conclusion, our data show that IFNγ-stimulated B cells strongly upregulate PD-L1, inhibit T<sub>FH</sub> cell responses and protect against atherosclerosis.</p>