Origins of Waldenstrom's macroglobulinemia: does it arise from an unusual B-cell precursor?
Clonotypic B cells of Waldenstrom's macroglobulinemia (WM) are CD20+ immunoglobulin (Ig) M+ IgD+ cells that lack ongoing somatic hypermutation and class switch recombination (CSR). Only a small compartment of clonotypic B cells express activation-induced cytosine deaminase. Activation by CD40L/interleukin-4 does not stimulate WM class switching. However, we found that the mutation of switch regions essential for CSR were present in IgM monoclonal gammopathy of unknown significance (MGUS) but absent from WM B cells, suggesting the possibility that not all IgM MGUS have the potential to give rise to WM, and further strengthening the hypothesis that the target cell in transformation to WM is an unusual type of B cell.
Kriangkum
Jitra
J
Department of Oncology, University of Alberta and Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
Taylor
Brian J
BJ
Reiman
Tony
T
Belch
Andrew R
AR
Pilarski
Linda M
LM
D000942:Antigens, Bacterial; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes; D002454:Cell Differentiation; D015321:Gene Rearrangement; D006801:Humans; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000276:immunology*; D009154:Mutation; D010265:Paraproteinemias / Q000276:immunology / Q000503:physiopathology; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*
D000942:Antigens, Bacterial; D018951:Antigens, CD20; C022863:H antigen; D007075:Immunoglobulin M