The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/4/1169/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 8, April 20, 1998 1169-1178

Articles

The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cµ–C{delta} Switch, and {lambda} Light Chain Expression

Christophe Arpin, Odette de Bouteiller, Diane Razanajaona, Isabelle Fugier-Vivier, Francine Brière, Jacques Banchereau, Serge Lebecque, and Yong-Jun Liu

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 {lambda} light chain expression and a Cµ–C{delta} 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 {lambda} light chain expression and a Cµ–C{delta} 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.

Address correspondence to Yong-Jun Liu, DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304-1104. Phone: 650-852-9196; Fax: 650-496-1200; E-mail: yliu{at}dnax.org

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.


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