title: CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase.
abstract: Occupancy of the B cell glycoprotein, CD72 results in syk-independent activation of phospholipase-C gamma and calcium mobilization. The cytoplasmic tail of CD72 does not contain an immunoreceptor tyrosine-based activation motif to directly transduce signals into the B lymphocyte. Hence, we investigated whether other coreceptors such as CD19 and its associated phosphatidylinositol 3-kinase (PI 3-K) were involved in CD72 signaling. Two specific inhibitors of PI 3-K inhibited CD72-stimulated B cell proliferation in a dose-dependent manner. Activation of B lymphocytes via CD72 resulted in recruitment and activation of PI 3-K, which was mediated by CD19. Accordingly, CD72 ligation induced CD19 tyrosine phosphorylation. Thus, lipid products generated as a result of PI 3-K activation may have an important function in CD72-mediated B lymphocyte activation. The kinetics of CD19 tyrosine phosphorylation induced by CD72 ligation were strikingly different from those seen following B cell antigen receptor (BCR) stimulation. A transient increase in the tyrosine phosphorylation of the complement receptors, CD21 and CD35 was observed in BCR- but not CD72-stimulated cells. Co-cross-linking of CD72 and CD19 failed to induce syk tyrosine phosphorylation suggesting that even under these conditions, CD72 signaling was independent of syk activation. A transient and stimulation-dependent physical association between CD19 and CD72 was observed in CD72-ligated cells. These observations suggest a mechanism by which CD72 can recruit CD19 and influence activation of CD19-associated PI 3-K, which appears to be critical for CD72-mediated B cell activation.
authors.affiliation: Department of Microbiology and Immunology, and Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
authors.forename: C
authors.initials: C
authors.lastname: Venkataraman
authors.forename: P J
authors.initials: PJ
authors.lastname: Lu
authors.forename: A M
authors.initials: AM
authors.lastname: Buhl
authors.forename: C S
authors.initials: CS
authors.lastname: Chen
authors.forename: J C
authors.initials: JC
authors.lastname: Cambier
authors.forename: S
authors.initials: S
authors.lastname: Bondada
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018941:Antigens, CD19 / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D007137:Immunoglobulin alpha-Chains / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D002867:Chromones; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007137:Immunoglobulin alpha-Chains; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D000072377:Syk Kinase; D014443:Tyrosine; D000077191:Wortmannin; C064228:CD72 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C000606896:SYK protein, human; C000606897:Syk protein, mouse