title: A differential requirement for phosphoinositide 3-kinase reveals two pathways for inducible upregulation of major histocompatibility complex class II molecules and CD86 expression by murine B lymphocytes.
abstract: Constitutive expression of major histocompatibility complex class II molecules (MHC II) is restricted to dendritic cells, cells of the macrophage lineage and B lymphocytes. In all three lineages, peptide fragments of captured antigen are loaded into newly synthesized MHC II molecules. In B-lineage cells, MHC II synthesis is dramatically increased on encounter with antigen, by T-cell-derived signals and by microbial products. We have previously shown that immature B cells fail to hyperexpress MHC II after antigen receptor [B-cell receptor (BCR)] ligation, but are responsive to other stimuli. Expression of the costimulatory molecule, CD86, was similarly regulated. This suggested the existence of two pathways regulating expression of these important molecules. Here we present data supporting this hypothesis. We show that activity of the enzyme phosphatidylinositol 3-kinase is critical for MHC II hyperexpression and induction of CD86 in response to ligation of the BCR or CD38, but not for responses to other stimuli including interleukin-4, lipopolysaccharide and CD40 ligation.
authors.affiliation: Department of Human Anatomy and Cell Biology, The University of Liverpool, UK. stumc@liv.ac.uk
authors.forename: Stuart
authors.initials: S
authors.lastname: Marshall-Clarke
authors.forename: Lynn
authors.initials: L
authors.lastname: Tasker
authors.forename: Mark P
authors.initials: MP
authors.lastname: Heaton
authors.forename: R Michael E
authors.initials: RM
authors.lastname: Parkhouse
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015854:Up-Regulation / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D002867:Chromones; D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000099192:CD69 Antigens; C497965:Cd86 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one