| Abstract
| - Abstract. We have previously shown that dual occupancy of sigM and CD40-essential receptors in T-dependent B cell responses-by antibodies held on CD32-L cells results in the rapid proliferation of resting human B Iymphocytes in a cytokine-Independentmanner. Here we report the detailed phenotype of blast population emerging in such cultrures.By 3 days the levels of CD19 and CD20 have increased 4- and 2-fold respectively: such high level expression of these two pan-B markers is characteristic of cells of germinal centre (GC) origin. B cells co-stimulated via sigM and CD40 express low level CD23 and almost hlf become CD5 +; they also acquire CD38 and-importantiy--CD77, both of these being selective markers of GC B cells. Expression of sigM and IgD is down-regulated on these cells and a minor, but significant, population of IgG+ cells appears,In marked contrast to GC B cells, the population proliferating in response to dual occupancy of sigM and IgD is down-regulation on these cells and a minor, but significiant, population of IgG+ cells appears.In marked contrast to GC B cells, the population prolifereting in response to dual occupance of sign and CD40 has up-regulated and strongly expresses CD44. Morphologically, the cells are heterogeneous but there is a dominant blastic cell type with relativelyscanty cytoplasm and having multiple nucleoll,both of which are characterstic of centroblasts; nevertheless, these cells remain morphologically distinct from freshly isolated GC B cells and show hallmark features of centrocytes. Although there is substantial cell death occurring by day 6-7 in these cultures, there is no morphologicl evidence for apoptosis. Thus, the proliferating population that emerges with some features of GC B cells but has others which are incompatible with that particular stage of differentiation. The possibility that it might represent (I)a blast stage that is transitional between activation in T zones and entry into the follicle or (ii) a precursor population that colonizes the primary follile prior to GC formation is discussed.
|
