FC-GAMMA-RIIB INHIBITS BOTH B-CELL-RECEPTOR-INDUCED AND CD19-INDUCED CA2-GAMMA-R-TRANSFECTED HUMAN B-CELLS( MOBILIZATION IN FC)

Fc gamma RIIb (CD32) controls antibody production by down-regulating c ell activation, when co-clustered with B cell antigen receptors (BOB) in vivo, via immune complexes consisting of secreted IgG and antigen, Fc gamma RIIb-BCR co-ligation in vitro was shown to inhibit the Ca2+ i nflux from the extracellular space, the mechanism of which is not full y understood, Human B cells express Fc gamma RIIb1 and Fc gamma RIIb2, differing only in a 19 amino acid long insert in the cytoplasmic tail of the former, To elucidate whether Fc gamma RIIb1 and Fc gamma RIIb2 isoforms show any difference in the down-regulation of B cells, we ha ve studied the effect of co-clustering of BCR and Fc gamma RIIb1 or Fc gamma RIIb2 on the Ca2+ signaling in a Burkitt's lymphoma cell line, ST486, transfected with the two isoforms respectively, We have shown h ere, for the first time, that co-aggregation of BCR and Fc gamma RIIb may also inhibit Ca2+ release from the endoplasmic reticulum pool of h uman B cells, Both isoforms mediated this inhibition and the inhibitor y effect depended on the ratio of BCR to Fc gamma RIIb cross-linking, In contrast to Fc gamma RIIb, the CD21/CD19 complex was shown to up-re gulate B cell response by lowering the activation threshold, We have s hown here that co-clustering of Fc gamma RIIb with CD19 inhibited the CD19-induced Ca2+ influx, Furthermore, the three party co-aggregation of Fc gamma RIIb with BCR and CD19 resulted in a decreased Ca2+ respon se, as compared to the BOB-plus CD19-induced one, indicating that Fc g amma RIIb may inhibit CD19-induced enhancement of B cell activation, O n the basis of these data we suggest that IgG-containing and C3d-fixin g immune complexes may down-regulate the B cell response by interferin g with both BCR-and CD19-mediated Ca2+ mobilization.