Identification of Plasma Cell Antigen PC-1 as a Novel Cell Surface Marker of Germinal Center, Memory and Plasmacytoma B Cells.

The murine plasma cell (PC) alloantigen PC-1, also known as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), is expressed on PCs and by many non-lymphoid tissues. PC-1 is best known for its role in phosphate metabolism, hydrolyzing NTP to generate pyrophosphate. However, its expression and function in B lymphocytes remains unclear. Here we describe a previously unknown expression pattern of PC-1 in murine late stage B cells and B lymphomas. In normal mice, expression of PC-1, determined by flow cytometry, was very low on bone marrow pro-B, pre-B, immature B, and mature B cells, and on splenic follicular and marginal zone B cells. However, peritoneal B cells expressed significantly higher levels of PC-1 than splenic naïve B cells. CD5⁺ B1a cells expressed more PC-1 than B1b and B2 cells. Interestingly, PC-1 distinguishes two subsets of B1a: PC-1^hi and PC-1^lo. The PC-1^hi B1a cells were IgM^lo, B220^lo, and larger in size while PC-1^lo B1a cells were IgM^hi, B220^hi, and smaller in size. The PC-1^hi B1a cells express higher levels of Blimp-1 transcripts than the PC-1^lo B1a cells, indicating that the PC- 1^hi B1a cells may exhibit features of pre-plasma cells. Furthermore, after immunization with NP-KLH, germinal center (GC) B cells, PCs and early memory B cells expressed 2–4-fold more PC-1 than naïve B cells. Naïve B cells stimulated with LPS or anti-IgM plus anti-CD40 antibodies also dramatically upregulated PC-1 expression. Finally, gene expression profiling studies of primary lymphomas in NFS.V(+) congenic mice revealed high expression levels of PC-1 in plasmacytomas, immunoblastic lymphomas, and centroblastic-follicular lymphoma types. These studies demonstrate that PC-1 can be a useful marker for identification of stages in GC and post-GC cell differentiation and of lymphomas with a GC or PC origin. The function of PC-1 in B cells is currently under investigation.