title: CD19 differentially regulates BCR signalling through the recruitment of PI3K.
abstract: CD19 is a co-stimulatory surface protein expressed exclusively on B cells and serves to reduce the threshold for signalling via the B-cell receptor (BCR). Co-ligation of CD19 with the BCR synergistically enhances mitogen-activated protein (MAP) kinase activity, calcium release and proliferation. We recently found that these parameters were also enhanced in CD19-null primary murine B cells following BCR ligation, suggesting a regulatory role for CD19 in BCR signalling. In this study, we demonstrate that the enhanced BCR signalling in the absence of CD19 was not dependent on the src kinase Lyn, but linked to phosphoinositide 3-kinase (PI3K) activity. Consistent with this, we detect PI3K associated with CD19 outside the lipid raft in resting B cells. Pre-ligation of CD19 to restrict its translocation with the BCR into lipid rafts attenuated BCR-induced PI3K and MAP kinase activation and subsequent B-cell proliferation. Thus, we propose that CD19 can modulate BCR signalling in both a positive and negative manner depending on the receptor/ligand interaction in vivo.
authors: The Walter and Eliza Hall Institute of Medical Research , Department of Medical Biology, The University of Melbourne , Australia .
authors: Yuekang
authors: Y
authors: Xu
authors: Kirsten
authors: K
authors: Fairfax
authors: Amanda
authors: A
authors: Light
authors: Nicholas D
authors: ND
authors: Huntington
authors: David M
authors: DM
authors: Tarlinton
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D004789:Enzyme Activation; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; C082599:protein-tyrosine kinase p55(blk); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: B-cell activation; co-receptor; signal transduction