Expression of Multiple Adhesion Molecules on Circulating Monoclonal B Cells in Myeloma

Abstract

Multiple myeloma is a tumor of the B cell lineage, with characteristic monoclonal end stage plasma cells in the bone marrow, responsible for producing large quantities of monoclonal immunoglobulin present in serum, and for triggering osteoclasts to produce lesions of the bone, leading to high blood calcium, the possibility of kidney failure, and severe pathological damage. The proliferative potential of these plasma cells is low, and they express very few surface molecules involved in locomotion and migration. Candidates for spreading of the disease are circulating, monoclonal B cells, which have been reported by us (1, 2) and others (3–8). We have described a large subset of circulating cells belonging to the same clone as the bone marrow plasma cells in myeloma, which represent late stages of B cell differentiation towards pre-plasma cells, predominantly expressing the CD45R0 isoform (1), only found on activated late stage B cells (9). This subset of monoclonal B cells in the peripheral blood was observed among newly diagnosed patients, as well as patients undergoing intermittent chemotherapy, or at stable phases of disease (1), and thus seems unaffected by conventional therapy (see also Pilarski et al., this issue). In contrast to the bone marrow plasma cells, the blood B cells comprise a proliferating subpopulation (2). The monoclonal B cells in the blood of myeloma patients are at a late stage of B cell differentiation, and appear to be continuously progressing towards the plasma cell stage. Significant numbers of plasma cells, however, are only found in the bone marrow, except in terminal or highly aggressive myeloma, where they may be present in the blood as well. These observations suggest that if the blood B cells are, or include, a precursor population for the bone marrow plasma cells of the same clonality, the blood B cells must be capable of extravasating and migration to the bone marrow. It further suggests that in myeloma patients, the blood does not provide the micro environmental stimuli to support the terminal differentiation to end stage plasma cells. The myeloma blood B cells express multiple adhesion molecules, including CD11b, L-Selectin, CD44, α2β1, and α6β1, in contrast to the plasma cells in the myeloma bone marrow. This strongly indicates that the circulating subset is indeed potentially more motile and capable of extravasating and homing to the bone marrow.