IFNγ-stimulated B cells inhibit T follicular helper cells and protect against atherosclerosis

Douna, H.; Mol, J. de; Amersfoort, J.; Schaftenaar, F.H.; Kiss, M.G.; Suur, B.E.; ... ; Foks, A.C. (2022)

Article / Letter to editor

B and T cells are interconnected in the T follicular helper-germinal center B cell (T_FH-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_FH-GC B cell axis can be achieved by providing negative co-stimulation to T_FH 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_FH cell development. To determine whether IFNγ-B cells can reduce collar-induced atherosclerosis, apoE ^-/- 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^hi 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_FH cell responses and protect against atherosclerosis.

• Cardiovascular disease
• Atherosclerosis, B cells
• PD-L1
• Interferon-gamma

• All authors: Douna, H.; Mol, J. de; Amersfoort, J.; Schaftenaar, F.H.; Kiss, M.G.; Suur, B.E.; Kroner, M.J.; Binder, C.J.; Bot, I.; Puijvelde, G.H.M. van; Kuiper, J.; Foks, A.C.
• Date: 2022-02-02
• Journal: Frontiers in Cardiovascular Medicine
• Volume: 9
• DOI: doi:10.3389/fcvm.2022.781436