The extrafollicular-to-follicular transition of human B lymphocytes: induction of functional globotriaosylceramide (CD77) on high threshold occupancyof CD40

Amongst lymphocytes, expression of CD77 (globotriaosylceramide, Gb3) is exc lusive to B cells of the germinal center (GC). Its acquisition by extrafoll icular B cells may thus herald their commitment to a follicular response. H ere we show that high threshold occupancy of CD40 by its cognate ligand (CD 40L) promotes rapid induction of CD77 expression in non-GC (CD38(lo)) B cel ls. The kinetics of CD77 acquisition mirrored those of GC-related markers C D95 and CD86 but contrasted with the more delayed increase in CD38 expressi on. Induction of CD77 was not a simple consequence of cell cycle entry: oth er conditions of stimulation equally capable of driving proliferation faile d to promote CD77 expression. CD77 was functional in that cells were now se nsitive to Verotoxin-l, an Escherichia coil-derived ligand of Gb3. These da ta indicate that acquisition by extrafollicular B cells of CD77 results fro m high threshold occupancy of CD40, a situation that should be reached phys iologically only once a critical level of T cell priming has been achieved.