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Selective expression of CD45 isoforms defines CALLA+ monoclonal B- lineage
cells in peripheral blood from myeloma patients as late stage B cells
GS Jensen, MJ Mant, AJ Belch, JR Berenson, BA Ruether and LM Pilarski
Department of Immunology, University of Alberta, Edmonton, Canada.
The peripheral blood lymphocytes from 42 patients with multiple myeloma
(MM) and 13 patients with monoclonal gammopathy of undetermined
significance (MGUS) were studied by three-color immunofluorescence (IF)
using antibodies directed to a broad range of B-cell markers (CD19, CD20,
CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high
and low molecular weight isoforms of the leukocyte common antigen, CD45RA
(p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells,
and a transition from CD45RA to CD45RO defines differentiation towards
plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with
myeloma included a large subset of B- lineage cells (mean of 39% to 45%)
that were CALLA+ and PCA-1+ in all patients studied, including newly
diagnosed patients and patients undergoing chemotherapy. Southern blot
analysis indicated the presence of monoclonal Ig rearrangements in PBMC and
a substantial reduction in the germ-line bands consistent with the presence
of a large monoclonal B-cell subset. Avoidance of purification methods
involving depletion of adherent cells was essential for detection of the
abnormal B cells. Phenotypically, this abnormal B-cell population
corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as
defined by the concomitant expression of low densities of CD19 and CD20,
moderate densities of CALLA and PCA-1, and strong expression of CD45RO on
all B cells, with weakly coexpressed CD45RA on a small proportion.
Heterogeneity in the expression of CD45RA and CD45RO within the abnormal
B-cell population from any given patient suggested multiple differentiation
stages. Abnormal B cells similar to those in MM were also detected in MGUS,
although as a lower proportion of PBMC (26%). Abnormal B cells from
patients with MGUS expressed predominantly the CD45RO isoform, but had a
lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from
MM. This work indicates that the large subset of circulating monoclonal B
lymphocytes from myeloma patients are at a late stage in B-cell
differentiation, continuously progressing towards the plasma cell stage.
Volume 78,
Issue 3,
pp. 711-719,
08/01/1991
Copyright © 1991 by The American Society of Hematology
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