title: Immunophenotypic analysis of B cells in PNH: insights into the generation of circulating naive and memory B cells.
abstract: 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(+)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 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.
authors.affiliation: Haematological Malignancy Diagnostic Service, Leeds General Infirmary, Leeds, United Kingdom. stephenr@pathology.leeds.ac.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Richards
authors.forename: G J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: P
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D000071178:CD48 Antigen; D002452:Cell Count; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006098:Granulocytes / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000071178:CD48 Antigen; D017261:Glycosylphosphatidylinositols; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7