The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression
Open Access
- 20 April 1998
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 187 (8), 1169-1178
- https://doi.org/10.1084/jem.187.8.1169
Abstract
Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient9s 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 λ light chain expression and a Cμ–Cδ 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 λ light chain expression and a Cμ–Cδ 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.Keywords
This publication has 61 references indexed in Scilit:
- Germinal Center Founder Cells Display Propensity for Apoptosis before Onset of Somatic MutationThe Journal of Experimental Medicine, 1997
- Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B CellsScience, 1996
- Reexpression of RAG-1 and RAG-2 Genes in Activated Mature Mouse B cellsScience, 1996
- Distinctive Features of Immunoglobulin Heavy Chain Variable Region Gene Rearrangement in Multiple MyelomaLeukemia & Lymphoma, 1994
- Markers of Multiple Hematopoietic-Cell Lineages in Multiple MyelomaNew England Journal of Medicine, 1990
- Class switch from μ to δ is mediated by homologous recombination between σμ and σμ sequences in human immunoglobulin gene lociEuropean Journal of Immunology, 1989
- Prognostic factors in IgD myeloma: A study of 21 casesScandinavian Journal of Haematology, 1984
- Membrane Ig on human lymphocytes: rate of turnover of IgD and IgM on the surface of human tonsil cellsEuropean Journal of Immunology, 1976
- Same Idiotypc of B-Lymphocyte Membrane IgD and IgM. Formal Evidence for Monoclonality of Chronic Lymphocytic Leukemia CellsScandinavian Journal of Immunology, 1974
- A NEW CLASS OF HUMAN IMMUNOGLOBULINSThe Journal of Experimental Medicine, 1965