Role of protein kinase activation in the induction of B cell adhesion by MHC class II ligands.
Engagement of MHC class II (Ia) molecules on B cells induces tyrosine phosphorylation, phosphoinositide turnover, elevation of intracellular calcium concentrations, and a rise in cAMP levels. However, a role for these biochemical signals in mediating functional responses induced by Ia ligands remains largely undefined. In this study, we utilized the induction of B cell adhesion by Ia ligands to demonstrate a role for signals transduced via Ia molecules in the generation of a functional response. Ia ligands that induced B cell aggregation induced tyrosine phosphorylation, whereas Ia ligands that did not induce B cell aggregation failed to induce any detectable tyrosine phosphorylation. Ia-induced B cell aggregation and tyrosine phosphorylation were inhibited by genistein and by herbimycin A, inhibitors of tyrosine kinases (PTK). Sphingosine and calphostin C, inhibitors of protein kinase C (PKC), also inhibited Ia-induced adhesion whereas HA1004, an inhibitor of cyclic nucleotide-dependent kinases, did not. Ia ligands induced both LFA-1-dependent and LFA-1-independent B cell adhesion. These two pathways of cell adhesion differed in their requirement for activation signals. PKC activation was sufficient for LFA-1-dependent adhesion, whereas LFA-1-independent adhesion required independent phosphorylation events mediated by PKC and by PTK. These results provide functional relevance for biochemical signals transduced via Ia molecules by demonstrating that Ia-induced B cell adhesion is mediated by the activation of PKC and by one or more PTK.
Fuleihan
R
R
Division of Immunology, Children's Hospital, Boston, MA 02115.
Spertini
F
F
Geha
R S
RS
Chatila
T
T
D001402:B-Lymphocytes / Q000502:physiology*; D016227:Benzoquinones; D002448:Cell Adhesion / Q000187:drug effects*; D004789:Enzyme Activation; D019833:Genistein; D006681:HLA-D Antigens / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013110:Sphingosine / Q000494:pharmacology
D016227:Benzoquinones; D006681:HLA-D Antigens; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013110:Sphingosine