MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis

Osteoclast-mediated bone erosion and deformation represent significant pathological features in rheumatoid arthritis (RA). Myeloid-derived suppressor cells (MDSCs) and B cells have emerged as key contributors to the progression of RA. Nevertheless, their involvement, especially the interaction in RA osteoclastogenesis remains elusive. In this study, our results revealed a marked expansion of MDSCs in RA patients, and importantly, their abundance was positively correlated with radiographic damage evaluated by the Sharp/van der Heijde score. Notably, MDSCs derived from both RA patients and arthritic mice exhibited a heightened propensity to differentiate into osteoclasts compared with those from healthy individuals. Intriguingly, we observed that B cells from RA patients could augment the osteoclastogenic potential of MDSCs, which was also observed in arthritic mice. The impact of B cells on MDSC-mediated osteoclastogenesis was found to be most pronounced in switched memory B cells, followed by CD21^low B cells and naïve B cells. MDSCs from B-cell-deficient mice exhibited diminished capacity to differentiate into osteoclasts, accompanied by distinct gene expression profiles associated with osteoclastogenesis. Taken together, our findings suggested that MDSCs were important osteoclast precursors primed by B cells in RA, serving as novel therapeutic targets for the persistent disease.