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In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+
peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain
[published erratum appears in Blood 1995 Jun 1;85(11):3365]
PL Bergsagel, AM Smith, A Szczepek, MJ Mant, AR Belch and LM Pilarski
Department of Immunology, University of Alberta, Edmonton, Canada.
Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the
bone marrow (BM). However, late-stage monotypic B cells have been detected
in the blood. This work analyzes the effects of clinical treatment on late
stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM
patients have 2 to 8 times as many circulating CD19+ cells as do normal
donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using
polymerase chain reaction indicates that the CD19+ population includes
cells sharing the same clonotypic CDR3 region as is detected in the BM
plasma cells, for patients analyzed during chemotherapy or in relapse. They
are also monotypic as defined by their cytoplasmic or surface expression of
Ig kappa or lambda light chain. The light chain restriction is the same as
that of the BM plasma cells. Individual patients observed over 1- to 2-year
periods exhibit considerable variation in the number of B cells present in
blood; this number does not correlate with the concentration of serum
monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any
of the chemotherapy regimens analyzed and remain at high levels during
transient remissions. Patients in the progressive phase of disease or in
relapse have significantly higher numbers of B cells than do patients in
transient remission or untreated patients. During periods when the quantity
of blood B cells approaches normal, phenotypically their quality is highly
abnormal, with physical and phenotypic heterogeneity. Most B cells express
CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or
pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude
that monoclonal B cells in the blood of myeloma patient populations include
drug-resistant reservoirs of clonotypic cells that may underlie relapse.
Volume 85,
Issue 2,
pp. 436-447,
01/15/1995
Copyright © 1995 by The American Society of Hematology
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