CD24hiCD38hi B regulatory cells from patients with end plate inflammation presented reduced functional potency.

Problem due to disc degeneration is frequently found in the aging population. However, severe pain and accompanying end plate inflammation is only found in a small subset of patients, who can be of a younger age than most people with severe disc degeneration, with no apparent cause. We hypothesized that deficiencies in B regulatory (Breg) cells might contribute to the aberrant inflammation in these patients. However, we found that the frequency of CD24hiCD38hi Breg cells was significantly higher in patients than in controls. To investigate Breg function, CD24hiCD38hi Breg cells were stimulated via CD40L/αIg and via Staphylococcus aureus Cowan. Interestingly, the expression of IL-10 and TGF-β1 was significantly lower in patients than in controls. The expression of PD-L1 was comparable between patient CD24hiCD38hi Bregs and control CD24hiCD38hi Bregs. Control CD24hiCD38hi Bregs, but not patient CD24hiCD38hi Bregs, could suppress the expression of TBX21 and RORC2 in stimulated CD4+ T cells, in a manner that was dependent on IL-10 and PD-L1. The expression of FOXP3, on the other hand, was dependent on TGF-β. In addition, PD-L1 reduced the viability of CD4+ T cells. Together, we demonstrated that the patients with end plate inflammation did not present a reduction in CD19+CD24hiCD38hi Breg frequency, but presented a reduction in CD19+CD24hiCD38hi Breg function.