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J. Exp. Med.,
Volume 187, Number 8, April 20, 1998 1169-1178
Switch, and 
Light Chain Expression
By
From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France
Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells
in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's
bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently
cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre-B cells, germinal center (GC) B cells, circulating memory cells, or
plasma blasts. This situation reflects what has been a general problem in cancer research for
years: how to compare a tumor with its normal counterpart. Although several studies have
demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a
biased 
light chain expression and a Cµ-C
isotype switch. Using surface markers, we have
previously isolated a population of surface IgM
IgD+CD38+ GC B cells that carry the most
impressive somatic mutation in their IgV genes. Here we show that this population of GC B
cells displays the two molecular features of IgD-secreting myeloma cells: a biased light chain
expression and a Cµ-C isotype switch. The demonstration of these peculiar GC B cells to
differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro
suggests that IgD-secreting plasma and myeloma cells are derived from GCs.
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