Plasma cell dyscrasias and normal plasma cells.

We have recently shown that two-color analysis with fluorescein isothiocyanate (FITC)-anti-CD38 antibody could clearly distinguish myeloma cells (plasma cells) from other hematopoietic cells in the bone marrow. Myeloma cells (plasma cells) alone were located at CD38strong positive(+++) fractions. We also identified two subpopulations among these myeloma cells: VLA-5-MPC-1- myeloma cells and VLA-5+MPC-1+ myeloma cells. Morphological examination showed that VLA-5- myeloma cells were mostly immature and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL-6), while VLA-5+ myeloma cells showed very low proliferation and no response to IL-6 but secreted higher amounts of M-protein in vitro significantly. Therefore, we could clarify heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA-5; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells. To further distinguish normal plasma cells from mature myeloma cells phenotypically, we examined immunophenotypes of normal plasma cells and myeloma cells by two-color flow cytometry with FITC-anti-CD38 antibody and phycoerythrin (PE) staining with a given antibody. Normal plasma cells in the bone marrow, tonsil, spleen and lymph node were all CD19+CD56-. On the other hand, mature myeloma cells were mostly CD19- and most of them were CD56+, and there were no myeloma cell with the CD19+CD56- phenotype. According to this findings, we investigated the expression of CD19 and CD56 on plasma cells (CD38+++ fractions) in benign monoclonal gammopathy (BMG). Both CD19+CD56- and CD19-CD56+ plasma cells were detected, and were suggesting that BMG consisted of phenotypically normal plasma cells and myeloma cells. In order to investigate from where myeloma cells (plasma cells) originate, the phenotypes of B cell lineage in tonsils, lymph nodes and peripheral blood were analyzed by two-color analysis. In the tonsils and lymph nodes, germinal center B cells (GC-B cells) revealed CD38+VLA-5-MPC-1-CD24-CD10+ CD5-, while the phenotype of mantle zone B cells (MZ-B cells) were CD38-VLA-5+ MPC-1+CD24+CD10-CD5+. On the other hand, we found CD38moderately positive(++) cells in the peripheral blood and they revealed VLA-5-MPC-1-CD24-CD10+CD5-. Morphological examination showed that these cells were plasmacytoid. Therefore, we regarded the cells as precursor plasma cells. In conclusion, we could present here that 1) myeloma cells consisted of VLA-5- immature and VLA-5+ mature myeloma cells, 2) normal plasma cells were clearly distinguished from mature myeloma cells phenotypically, 3) plasma cells in BMG contained both normal plasma cells and myeloma cells, 4) precursor plasma cells were identified in the peripheral blood.