Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease

Figure 3

Examples of potential signaling mechanisms involved in the O-glycosylation of IgA1. Several signaling mechanisms likely regulate O-glycosylation patterns of IgA1 in the Golgi apparatus. In this scheme, we have highlighted examples of three types of signaling systems that are potential players in the production of galactose-deficient IgA1 (Gd-IgA1). BAFF signaling through the BAFF receptor(s) (TACI, BAFF-R, and BCMA/TRAF) prevents degradation of NF-κB and enhances its subsequent translocation to the nucleus. This mechanism represents an example of a signaling pathway related to survival and proliferation of cells producing Gd-IgA1. Cytokine LIF, that binds the LIF-R/gp130 receptor complex, signals in B cells through STAT1 phosphorylation by JAK, followed by dimerization and translocation of the active STAT dimers to the nucleus. IL-6 activates the STAT3 pathway in B cells via JAK activation at the IL-6/gp130 complex. LIF and IL-6 signaling pathways are examples of a mechanism by which environmental factors may alter expression of specific glycosyltransferases. Activation of the MAPK pathways through various intraextracellular mechanisms can lead directly to the Golgi apparatus. MAPK signaling in B cells is another example of a pathway for an environment-mediated influence to change expression of specific glycosyltransferases, to signal directly to the Golgi apparatus, or both.