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

Area of Science:

• Immunology
• Cardiovascular Disease Research

Background:

• The T follicular helper-germinal center B cell (T_FH-GC B cell) axis is hyperactive in atherosclerosis.
• Loss of control in this axis exacerbates atherosclerosis.
• The PD-1/PD-L1 pathway offers a target for inhibiting T_FH cells.

Purpose of the Study:

• To investigate a novel therapeutic strategy using PD-L1-expressing B cells to inhibit atherosclerosis.
• To determine if IFNγ-stimulated B cells can reduce atherosclerosis by modulating the T_FH-GC B cell axis.

Main Methods:

• Utilized apoE ^-/- mice fed a Western-type diet.
• Administered phosphate-buffered saline (PBS), B cells, or IFNγ-stimulated B cells (IFNγ-B cells) post-carotid artery collar placement.
• Analyzed T_FH cell development, B cell populations (GC B cells, plasmablasts), regulatory T cells (Tregs), IL-10 production, and atherosclerotic lesion volume.

Main Results:

• IFNγ-B cells significantly increased PD-L1 expression on B cells and GC B cells.
• IFNγ-B cells treatment reduced T_FH cell development and plasmablasts.
• IFNγ-B cells promoted atheroprotective Tregs and T cell-derived IL-10.
• IFNγ-B cells significantly reduced atherosclerotic lesion volume in carotid arteries.

Conclusions:

• IFNγ-stimulated B cells upregulate PD-L1, effectively inhibiting T_FH cell responses.
• This strategy demonstrates a protective effect against atherosclerosis in a mouse model.
• IFNγ-B cells represent a promising therapeutic approach for atherosclerosis.