Figure 2.

Role of TACI in B cell physiology and MM pathophysiology. For normal B cells, TACI regulate immunoglobulin class switching upon engagement by BAFF or APRIL. It transduces the activation signals via interacting with adaptor protein MyD88 and cooperates with signaling through TLRs, such as TLR4, to promote immunoglobulin class switching. TACI can also regulate plasma cell differentiation and survival by upregulating transcriptional factors Blimp-1 and XBP-1 and downregulating pro-apoptotic protein Bim. For pathogenesis of MM, TACI mediates the signals of BAFF and APRIL to activate multiple downstream signaling pathways, including NF-κB, PI3k/Akt, and MAPKs pathways, leading to upregulation of anti-apoptotic proteins BCL-2 and MCL-1, which enhance MM cell survival. TACI-mediated signaling can also support immunosuppressive tumor microenvironment in the bone marrow of MM patients by promoting the survival of regulatory T cells and their inhibitory functions.