Increased Expression of BCMA on Systemic Lupus Erythematosus B Cells is Associated with Enhanced Response to CpG (99.43)

Abstract

Abstract BLyS and APRIL are members of the TNF superfamily that regulate B cell survival and autoreactivity, and can exist as homotrimers or BLyS/APRIL heterotrimers (HT). To further understand BLyS and APRIL function in SLE, we examined the expression profiles of their receptors (BAFF-R, TACI and BCMA) and their functional effects on B cell subsets. Whereas BAFF-R expression on SLE B cells was significantly lower compared to its levels on healthy control B cells (MFI of control vs SLE, naïve=1387 vs 929, p=0.002; memory=1290 vs 840, p=0.003), BCMA expression was substantially higher on SLE B cells (MFI of control vs SLE: 18 vs 28, p=0.038). This was most pronounced in the memory B cell subset (MFI of control vs SLE=19 vs 29, p=0.008) but was also evident on certain subsets of CD27- B cells. BCMA+ cells were mostly IgD+ and tended to be larger than BCMA-negative cells, and had higher CD19 and CD86 expression, indicating a greater degree of activation. FACS sorted BCMA+ B cells proliferated and differentiated much more potently than BCMA- B cells following CpG stimulation. CpG mainly induced the proliferation of BCMA+ B cells and increased BCMA expression on total B cells. These findings may help to explain the observed expansion of DNA-reactive SLE B cells in the presence of BLyS, APRIL or HT.