Differential calcium signaling by IgM- and IgD-BCRs 9188

Abstract Description Naive B cells coexpress two kinds of BCRs - IgM and IgD. IgD-BCR promotes tolerance to self antigens, whereas IgM-BCR triggers activation signaling. However, the signaling differences between the two BCRs are not fully understood. In this study, we stimulated follicular B cells with anti-IgM, anti-IgD, or both, to investigate calcium signaling, phosphorylation of Syk and BTK, and cell survival. Engagement of IgM or IgD BCRs revealed distinct intracellular calcium signaling patterns. Anti-IgM antibody stimulation induced a sustained increase in intracellular calcium, whereas anti-IgD Ab caused a rapid increase followed by a sharp decline of intracellular calcium. This difference was observed even with depletion of extracellular calcium, suggesting ER calcium was differentially regulated by IgM- or IgD-BCRs. Simultaneous engagement of IgM- and IgD-BCRs resulted in a pattern similar to that of IgD-BCR engagement alone, indicating IgD-BCR signaling inhibits IgM-BCR signaling. IgM- and IgD-BCR complexes appear to be differentially regulated, as IgD engagement caused downregulation of CD19 and CD23 compared to IgM-BCR. The IgD-BCR, but not IgM-BCR, engagement failed to sustain B cell survival. In summary, IgM and IgD-BCRs were differentially associated with co-receptors and induced distinct calcium signaling patterns. These findings offer insights into the differential functions of IgM- and IgD-BCRs. Funding Sources Supported by 2023R1A2C2004510; RS-2024-00405650 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)