Adhesion of multiple myeloma peripheral blood B cells to bone marrow fibroblasts: A requirement for CD44 and alpha(4)beta(7)

We have earlier described the presence of phenotypically unusual monoclonal B cells within the peripheral blood of multiple myeloma (MM) patients, To determine the biological properties of these B cells as compared to B cells from normal donors, we investigated the potential of CD19(+) MM blood B cells to adhere to endothelial cell and bone marrow (BM)-fibroblast monolayers. We find that 30-60% of freshly isolated CD19(+) MM blood B cells adhere to endothelial cell monolayers, and 50-80% adhere to BM fibroblast monolayers. The adhesion of MM blood B cells to either monolayer was not increased by in vitro activation, suggesting that these cells were activated in vivo. In contrast, fewer than 10% of CD19(+) B cells from peripheral blood of normal donors adhered, Function-blocking monoclonal antibodies (mAbs) were used to determine which adhesion receptors were involved in CD19(+) MM blood B cell interaction with BM fibroblasts. mAbs against very late antigen 4, the beta(7)-integrin subunit, and CD44, but not mAbs against very late antigen 5 and beta(1), inhibited adhesion 61, 50, and 30%, respectively, The lack of inhibition with mAbs against beta(1) implicates alpha(4) beta(7) but not alpha(4) beta(1) in adhesion of CD19(+) MM blood B cells, To determine the alpha(4) beta(7) ligand that mediated MM blood B cell adhesion, mAbs against vascular cellular adhesion molecule 1 and fibronectin, as well as CSI and RGD peptides, were used as inhibitors. These were unable to reduce the adhesion of CD19(+) MM blood B cells to BM fibroblasts, suggesting that fibronectin and vascular cellular adhesion molecule 1 are not involved in adhesion, Also, adhesion of MM blood B cells to mucosal addressin cell adhesion molecule 1-transfected Chinese hamster ovary cells was not enhanced compared to control-transfected Chinese hamster ovary cells, suggesting that mucosal addressin cell adhesion molecule I was not promoting adhesion of these cells. These data implicate CD44:HA interactions, as well as alpha(4) beta(7) and an as yet unidentified ligand in the adhesion of in vivo activated MRI blood B cell adhesion to BM fibroblasts. The adhesion properties of MM CD19(+) B cells distinguishes them from normal B cells, Although the malignant status of these cells is as yet undefined, their adhesion properties implicate MM blood B cells in migratory spread of the disease.