title: Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD(+)CD27(+) memory B cells.
abstract: Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare disorder of unknown aetiology affecting predominantly young to middle-aged women. It is characterized by a polyclonal expansion of B cells, including typical binucleated lymphocytes, and is associated with the presence of the translocation t(14;18), involving the bcl-2 oncogene. The stage of differentiation of the B cells expanded in PPBL is not known. We analysed the immunophenotype of the expanded B-cell subset in five new patients with PPBL and found a large uniform expansion of a recently defined human memory B-cell population, IgD(+)CD27(+) memory B cells. After in vitro stimulation with interleukin 2 (IL-2) and Staphylococcus aureus Cowan strain I, B cells from PPBL patients produced high levels of IgM immunoglobulins, which is a characteristic feature of IgD(+)CD27(+) memory B cells. Using a quantitative real-time polymerase chain reaction method, we found a high frequency of the translocation t(14;18) in the range of 1000-3000 per 106 B cells in PPBL patients. In contrast, a much smaller number of cells with a t(14;18) was found in B cells from healthy individuals. Our finding that PPBL is an accumulation of memory B cells further suggests that chronic antigeneic stimulation plays an important part in the pathogenesis of this disorder. This IgD(+)CD27(+) memory B-cell population might harbour a certain number of 'physiological' t(14;18) translocations that increases as this population expands in PPBL patients and constitutes the majority of peripheral blood lymphocytes.
authors.affiliation: Laboratory of Oncology, Department of Internal Medicine, University Hospital Zürich, Zürich, Switzerland. andreas.himmelmann@dim.usz.ch
authors.forename: A
authors.initials: A
authors.lastname: Himmelmann
authors.forename: O
authors.initials: O
authors.lastname: Gautschi
authors.forename: M
authors.initials: M
authors.lastname: Nawrath
authors.forename: U
authors.initials: U
authors.lastname: Bolliger
authors.forename: J
authors.initials: J
authors.lastname: Fehr
authors.forename: R A
authors.initials: RA
authors.lastname: Stahel
mesh_terms: D000328:Adult; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002999:Clone Cells; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D008218:Lymphocytosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013211:Staphylococcus aureus; D014178:Translocation, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein