Immunophenotypic analysis of B cells in PNH: insights into the generation of circulating naive and memory B cells

Peripheral blood B cells in patients with paroxysmal nocturnal hemoglobinur ia (PNH) comprise variable mixtures of normal B cells produced before the o nset of disease and glycosylphosphatidylinositol (GPI)-deficient B cells de rived from the PNH hematopoietic stem cell. In a detailed phenotypic analys is of 29 patients with PNH, this study shows consistent phenotypic differen ces between PNH B cells and residual normal B cells. In the majority of pat ients with active disease, PNH B cells comprised mainly naive cells with a CD27(-)IgM(+)IgD(strong+)IgG(-) phenotype. The proportion of CD27(+) memory cells within this compartment was related to disease duration (Spearman [r (s)] 0.403; P = .030), In PNH patients with predominantly GPI-deficient hem atopoiesis, that is, a large granulocyte PNH clone, the residual normal B c ells had a predominantly memory (CD27(+)) phenotype. Furthermore, the major ity of these memory B cells were not immunoglobulin tig) class switched and had an IgM(+)IgD(+)IgG(-) phenotype. Using PNH as a novel model with which to study B lymphopoiesis, this study provides direct evidence that product ion of new naive B cells occurs throughout life and that the major populati on of long-lived memory B cells are IgM(+)IgD(+). Moreover, studies of GPI( -) B cells in 2 patients in remission from PNH suggest that the life span o f a B-cell clone can be more than 24 years. (C) 2000 by The American Societ y of Hematology.