Fc gammaRIIb inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in Fc gammaR-transfected human B cells |
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Authors: | Koncz, G Gergely, J Sarmay, G |
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Affiliation: | Department of Immunology, Lorand Eotvos University, God, Hungary. |
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Abstract: | Fc gammaRIIb (CD32) controls antibody production by down-regulating cellactivation, when co-clustered with B cell antigen receptors (BCR) in vivo,via immune complexes consisting of secreted IgG and antigen. FcgammaRIIb-BCR co-ligation in vitro was shown to inhibit the Ca2+ influxfrom the extracellular space, the mechanism of which is not fullyunderstood. Human B cells express Fc gammaRIIb1 and Fc gammaRIIb2,differing only in a 19 amino acid long insert in the cytoplasmic tail ofthe former. To elucidate whether Fc gammaRIIb1 and Fc gammaRIIb2 isoformsshow any difference in the down-regulation of B cells, we have studied theeffect of co-clustering of BCR and Fc gammaRIIb1 or Fc gammaRIIb2 on theCa2+ signaling in a Burkitt's lymphoma cell line, ST486, transfected withthe two isoforms respectively. We have shown here, for the first time, thatco- aggregation of BCR and Fc gammaRIIb may also inhibit Ca2+ release fromthe endoplasmic reticulum pool of human B cells. Both isoforms mediatedthis inhibition and the inhibitory effect depended on the ratio of BCR toFc gammaRIIb cross-linking. In contrast to Fc gammaRIIb, the CD21/CD19complex was shown to up-regulate B cell response by lowering the activationthreshold. We have shown here that co-clustering of Fc gammaRIIb with CD19inhibited the CD19-induced Ca2+ influx. Furthermore, the three partyco-aggregation of Fc gammaRIIb with BCR and CD19 resulted in a decreasedCa2+ response, as compared to the BCR- plus CD19-induced one, indicatingthat Fc gammaRIIb may inhibit CD19- induced enhancement of B cellactivation. On the basis of these data we suggest that IgG-containing andC3d-fixing immune complexes may down- regulate the B cell response byinterfering with both BCR- and CD19- mediated Ca2+ mobilization. |
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