Interaction of signaling molecules with human Fc gamma RIIb1 and the role of various Fc gamma RIIb isoforms in B-cell regulation.
The low-affinity type-IIb IgG Fc-binding receptors (Fc gamma RIIb) are expressed on B cells. When cross-linked with mIgM Fc gamma RIIb are known to down-regulate B-cell activation by interrupting signal transduction upstream from G-protein-activated events. We have studied Fc gamma RII isoforms expressed on resting and activated B cells and the interaction of Fc gamma RIIb1 with molecules transducing the antigen receptor-mediated signals. Expression of Fc gamma RII isoforms was studied by reverse transcription and polymerase chain reaction. Resting B cells express both Fc gamma RIIb2 and Fc gamma RIIb1 isoforms. Activation with anti-IgM or IL-4 induces the splicing of Fc gamma RIIb1 mRNA, while the alternative splicing of Fc gamma RIIb2 mRNA is down-regulated, resulting in the surface expression of Fc gamma RIIb1. Functional differences were found between the two isoforms in inhibiting B-cell activation, suggesting that Fc gamma RIIb2 might influence the threshold of signals necessary for activation of resting B cells, while Fc gamma RIIb1 may regulate in later phases of antibody response. To explore the mechanism by which Fc gamma RII may uncouple antigen receptor-mediated signal transduction, we have investigated the association of signaling molecules with Fc gamma RII. Beside the protein tyrosine kinase (PTK) fyn, protein kinase C (PKC) was found to be co-isolated with Fc gamma RIIb1, suggesting a tight connection between these kinases and Fc gamma RII. We suggest that PKC might be responsible for the activation-induced phosphorylation of Fc gamma RII on serine residues.(ABSTRACT TRUNCATED AT 250 WORDS)
Sarmay
G
G
Laboratory of Immunoregulation, Vienna International Research Cooperation Center, Sandoz Forschungsinstitut, Austria.
Rozsnyay
Z
Z
Koncz
G
G
Gergely
J
J
D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D006801:Humans; D008213:Lymphocyte Activation; D018448:Models, Immunological; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D011493:Protein Kinase C