Restricted Expression of Immunoglobulin Light Chain mRNA and of the Adhesion Molecule CD11b on Circulating Monoclonal B Lineage Cells in Peripheral Blood of Myeloma Patients

Abstract

Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetertmined siginificance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0⁺, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either K or λ light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour related circulating B cells express high densities of CD11b, a β₂-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimutation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19⁺ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b⁺ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19⁺ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulaling myeloma B cells to the bone marrow.