Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients—diagnostic and clinical implications

Abstract

SUMMARYHuman MM is a haematologic disorder characterized by the accumulation of malignant plasma cells (PC), primarily in the bone marrow (BM). Although these cells characteristically home to the BM, in recent years several groups have detected the presence of related malignant B cells in the peripheral blood (PB) which could be implicated in the progression and spread of the disease. However, the proportion and origin of these clonotypic circulating B cells is still controversial. In this study, using a triple-staining flow cytometric procedure and a whole blood lysis method, PB B lineage cells could be divided into two populations according to their distinct repertoires of cell adhesion molecules and B cell antigens in untreated MM patients. The results show that: (i) the percentage and the absolute number of PB CD19þ B cells were decreased in MM patients compared with controls; (ii) the quantity and percentage of B cell antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (b 1 -and b 2 -integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19 þ cells of MM patients and healthy subjects were similar and all of them were virtually polyclonal cells; (iii) a very minor circulating CD19 -CD38 þþ CD45 ¹/dim subset was also detected which expressed CD138 (B-B4) (high intensity), monoclonal cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19, CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such as CD62L, CD18 and CD11a; this CD19 -CD38 þþ CD45 -/dim CD138 þþ subset was not found in normal blood and exhibited a phenotypic profile which was closely related to that of malignant BM plasma cells, with the exception of the CD56 antigen. Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements confirmed these results. We postulate that, in MM patients, circulating B lineage cells may be divided into two different categories: polyclonal CD19 þ B cells and a very minor proportion of clonal CD138 þþ PC that escape from the BM.

Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma

“…10 Alternatively, our results could also indicate that in order to spread the diseaseFlike normal BM PC 23,32,42 Fclonal PC could also leave the BM, recirculate into PB and home again into the BM at a different localization, in a kind of 'metastatic'/dissemination process. In line with this hypothesis, in this and other studies [7][8][9][10][11][12][13][14]43 circulating clonal PC were detected in a significant proportion of MGUS and SMM cases in addition to MM. A potential explanation for the recirculation of clonal PC in the early stages of the disease (for example, MGUS) could rely on the advanced age of MGUS patients, which could lead to lower numbers of available BM niches.…”

“…5,6 Despite the different tumor mass [7][8][9][10][11][12][13][14] and clinical behavior of the disease, clonal PC from MGUS, SMM and MM patients show highly similar and largely overlapping genetic profiles. [15][16][17] In addition, no clear phenotypic differences have been reported so far among clonal PC from MGUS, SMM and MM, 18 except for a few molecules involved in the interaction between PC and their microenvironment.…”

Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus

“…All cells expressing intracellular Ig are CD19 dim (data not shown). The expression of CD19 on peripheral plasma cells has been shown before (49,50) and contrasts with the apparent absence of CD19 on myeloma cells (50,51). Only two-thirds of them also express CD138 ϩ (syndecan-1).…”

Plasma cell purification from murine bone marrow using a two-step isolation approach

“…Lack of identifying cell surface molecules makes it difficult to isolate a pure population of plasma cells. One unique feature of plasma cells is the expression of relatively high levels of CD138 (Syndecan-1), which has proven to be an effective means of identifying antibody secreting cells in vivo in both humans and mouse (Sanderson et al, 1989;Luque et al, 1998). Using CD138 expression has been less successful for purifying plasma cells directly from bone marrow for use ex vivo because the frequency of plasma cells is rare.…”