ENPP1-positive B cells and activation in human peripheral blood (LYM6P.772)

Abstract

Abstract ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1), also known as PC1 (plasma cell alloantigen 1), is a homodimeric type II transmembrane glycoprotein that mediates nucleotide recycling by breaking down ATP to AMP. Previous studies of mouse B lineage cells showed that levels of PC1 expression could distinguish two distinct subsets of peritoneal B -1a cells. In addition, PC1 expression increases progressively on germinal center B cells and splenic plasma cells with highest levels on bone marrow plasma cells. To determine if PC1 might also help define human B1-like cells, we have used a mouse mAb to human PC1 to characterize its expression on human cells. The frequency of PC1-positive cells from cord blood (mean 6%, n=10) was higher than that from adult peripheral blood (1.34%, n=15). These PC1-positive cells are mostly derived from CD27- naïve B cells expressing CD38, IgM and IgD, and were detected in plasmablast/plasma cells in peripheral blood. In contrast to B-1a cells in mice, human PC1-positive cells did not secrete natural Abs or produce IL10. Expression of PC1 was greatly increased on purified peripheral blood B cells stimulated with anti-CD40, IL4 and IL21. These activated PC1-positive cells expressed low levels of CD5, HLA-DR, surface IgM, and high levels of B cell activation markers and CD138. Our results indicated that PC1-positive B cell populations in humans are different from either CD20+CD27+CD43+ B1 cells in human, or CD5+ B-1a cells in mice.