|
||
Articles |
Switch, and
Light Chain Expression
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.
1Abbreviations used in this paper: CDR, complementarity determining region; GC, germinal center; s, surface.
C. Arpin is the recipient of a grant from the Fondation Mérieux (Lyon, France).
Jacques Banchereau's present address is the Baylor Institute of Immunology Research, 3535 Worth St., Sammons Cancer Center, Suite 4800, Dallas, TX 75246.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
| TABLE OF CONTENTS |
|