CD24^hiCD38^hi 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 CD24^hiCD38^hi Breg cells was significantly higher in patients than in controls. To investigate Breg function, CD24^hiCD38^hi 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 CD24^hiCD38^hi Bregs and control CD24^hiCD38^hi Bregs. Control CD24^hiCD38^hi Bregs, but not patient CD24^hiCD38^hi 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⁺CD24^hiCD38^hi Breg frequency, but presented a reduction in CD19⁺CD24^hiCD38^hi Breg function.