Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD(+)CD27(+) memory B cells

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare disorder of unk nown aetiology affecting predominantly young to middle-aged women. It is ch aracterized by a polyclonal expansion of B cells, including typical binucle ated lymphocytes, and is associated with the presence of the translocation t(14;18), involving the bcl-2 oncogene. The stage, of differentiation of th e 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 lar ge 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 patient s produced high levels of IgM immunoglobulins, which is a characteristic fe ature of IgD(+)CD27(+) memory B cells. Using a quantitative real-time polym erase chain reaction method, we found a high frequency of the translocation t(15; 18) in the range. of 1000-3000 per 10(6) B cells in PPBL patients. I n contrast, a much smaller number of cells with a t(14;18) was found in B c ells from healthy individuals. Our finding that PPBL is an accumulation of memory B cells further suggests that chronic antigeneic stimulation plays a n important part in the pathogenesis of this disorder. This IgD(+)CD27(+) m emory B-cell population might harbour a certain number of 'physiological' t (14;18) translocations that increases as this population expands in PPBL pa tients and constitutes the majority of peripheral blood lymphocytes.