Fc gammaRIIb inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in Fc gammaR-transfected human B cells.
Fc gammaRIIb (CD32) controls antibody production by down-regulating cell activation, when co-clustered with B cell antigen receptors (BCR) in vivo, via immune complexes consisting of secreted IgG and antigen. Fc gammaRIIb-BCR co-ligation in vitro was shown to inhibit the Ca2+ influx from the extracellular space, the mechanism of which is not fully understood. Human B cells express Fc gammaRIIb1 and Fc gammaRIIb2, differing only in a 19 amino acid long insert in the cytoplasmic tail of the former. To elucidate whether Fc gammaRIIb1 and Fc gammaRIIb2 isoforms show any difference in the down-regulation of B cells, we have studied the effect of co-clustering of BCR and Fc gammaRIIb1 or Fc gammaRIIb2 on the Ca2+ signaling in a Burkitt's lymphoma cell line, ST486, transfected with the two isoforms respectively. We have shown here, for the first time, that co-aggregation of BCR and Fc gammaRIIb may also inhibit Ca2+ release from the endoplasmic reticulum pool of human B cells. Both isoforms mediated this inhibition and the inhibitory effect depended on the ratio of BCR to Fc gammaRIIb cross-linking. In contrast to Fc gammaRIIb, the CD21/CD19 complex was shown to up-regulate B cell response by lowering the activation threshold. We have shown here that co-clustering of Fc gammaRIIb with CD19 inhibited the CD19-induced Ca2+ influx. Furthermore, the three party co-aggregation of Fc gammaRIIb with BCR and CD19 resulted in a decreased Ca2+ response, as compared to the BCR- plus CD19-induced one, indicating that Fc gammaRIIb may inhibit CD19-induced enhancement of B cell activation. On the basis of these data we suggest that IgG-containing and C3d-fixing immune complexes may down-regulate the B cell response by interfering with both BCR- and CD19-mediated Ca2+ mobilization.
Koncz
G
G
Department of Immunology, Loránd Eötvös University, Göd, Hungary.
Gergely
J
J
Sármay
G
G
D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D018941:Antigens, CD19; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D002118:Calcium