Blood, 15 November 2000, Vol. 96, No. 10, pp. 3522-3528
IMMUNOBIOLOGY
Immunophenotypic analysis of B cells in
PNH: insights into the generation of circulating
naive and memory B cells
Stephen J. Richards,
Gareth J. Morgan, and
Peter Hillmen
From the Haematological Malignancy Diagnostic Service,
Leeds General Infirmary, Leeds, United Kingdom.
Peripheral blood B cells in patients with paroxysmal nocturnal
hemoglobinuria (PNH) comprise variable mixtures of normal B cells
produced before the onset of disease and glycosylphosphatidylinositol (GPI)-deficient B cells derived from the PNH hematopoietic stem cell.
In a detailed phenotypic analysis of 29 patients with PNH, this study
shows consistent phenotypic differences between PNH B cells and
residual normal B cells. In the majority of patients with active
disease, PNH B cells comprised mainly naive cells with a
CD27
IgM+IgDstrong+IgG
phenotype. The proportion of CD27+ memory cells within this
compartment was related to disease duration (Spearman
[rs] 0.403; P = .030). In PNH patients with
predominantly GPI-deficient hematopoiesis, that is, a large granulocyte
PNH clone, the residual normal B cells had a predominantly memory (CD27+) phenotype. Furthermore, the majority of these
memory B cells were not immunoglobulin (Ig) 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 production of new naive B cells occurs
throughout life and that the major population 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 of a B-cell clone can be more than 24 years.
