title: The extrafollicular-to-follicular transition of human B lymphocytes: induction of functional globotriaosylceramide (CD77) on high threshold occupancy of CD40.
abstract: Amongst lymphocytes, expression of CD77 (globotriaosylceramide, Gb3) is exclusive to B cells of the germinal center (GC). Its acquisition by extrafollicular B cells may thus herald their commitment to a follicular response. Here we show that high threshold occupancy of CD40 by its cognate ligand (CD40L) promotes rapid induction of CD77 expression in non-GC (CD38(lo)) B cells. The kinetics of CD77 acquisition mirrored those of GC-related markers CD95 and CD86 but contrasted with the more delayed increase in CD38 expression. Induction of CD77 was not a simple consequence of cell cycle entry: other conditions of stimulation equally capable of driving proliferation failed to promote CD77 expression. CD77 was functional in that cells were now sensitive to Verotoxin-1, an Escherichia coli-derived ligand of Gb3. These data indicate that acquisition by extrafollicular B cells of CD77 results from high threshold occupancy of CD40, a situation that should be reached physiologically only once a critical level of T cell priming has been achieved.
authors.affiliation: MRC Centre for Immune Regulation The University of Birmingham, Birmingham, GB.
authors.forename: N
authors.initials: N
authors.lastname: McCloskey
authors.forename: J D
authors.initials: JD
authors.lastname: Pound
authors.forename: M J
authors.initials: MJ
authors.lastname: Holder
authors.forename: J M
authors.initials: JM
authors.lastname: Williams
authors.forename: L M
authors.initials: LM
authors.lastname: Roberts
authors.forename: J M
authors.initials: JM
authors.lastname: Lord
authors.forename: J
authors.initials: J
authors.lastname: Gordon
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D002453:Cell Cycle / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007739:L Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009244:NAD+ Nucleosidase / Q000096:biosynthesis; D014066:Palatine Tonsil; D013997:Time Factors; D014281:Trihexosylceramides / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D019014:fas Receptor / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D014281:Trihexosylceramides; D019014:fas Receptor; D023201:CD40 Ligand; C018549:globotriaosylceramide; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1