Interaction of signaling molecules with human FcγRIIb1 and the role of various FcγRIIb isoforms in B-cell regulation

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Abstract

The low-affinity type-IIb IgG Fc-binding receptors (FcγRIIb) are expressed on B cells. When cross-linked with mIgM FcγRIIb are known to down-regulate B-cell activation by interrupting signal transduction upstream from G-protein-activated events. We have studied FcγRII isoforms expressed on resting and activated B cells and the interaction of FcγRIIb1 with molecules transducing the antigen receptor-mediated signals. Expression of FcγRII isoforms was studied by reverse transcription and polymerase chain reaction. Resting B cells express both FcγRIIb2 and FcγRIIb1 isoforms. Activation with anti-IgM or IL-4 induces the splicing of FcγRIIb1 mRNA, while the alternative splicing of FcγRIIb2 mRNA is down-regulated, resulting in the surface expression of FcγRIIb1. Functional differences were found between the two isoforms in inhibiting B-cell activation, suggesting that FcγRIIb2 might influence the threshold of signals necessary for activation of resting B cells, while FcγRIIb1 may regulate in later phases of antibody response. To explore the mechanism by which FcγRII may uncouple antigen receptor-mediated signal transduction, we have investigated the association of signaling molecules with FcγRII. Beside the protein tyrosine kinase (PTK) fyn, protein kinase C (PKC) was found to be co-isolated with FcγRIIb1, suggesting a tight connection between these kinases and FcγRII. We suggest that PKC might be responsible for the activation-induced phosphorylation of FcγRII on serine residues. Signaling molecules responsible for the activation and localization of further elements of the activation pathway were also found to associate with FcγRII. Among these RasGAP and Shc, the adapter molecule connecting PTK-triggered events to the Ras activation-dependent pathway were characterized. We suggest that FcγRII may compete with the B-cell antigen receptor for key molecules regulating Ras activity, inhibiting thereby Ras activation.

Original languageEnglish
Pages (from-to)125-131
Number of pages7
JournalImmunology letters
Volume44
Issue number2-3
DOIs
Publication statusPublished - Jan 2 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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