The Contribution of Immunoglobulin G to Inflammation is Regulated by The Site of Production via Glycosylation

Authors : Altan Ercan

Pages : 918-935

View : 30 | Download : 50

Publication Date : 2025-12-31

Article Type : Research Paper

Abstract :Immunoglobulin G (IgG) is one of the main contributors to inflammation due to its function and amount in circulation. This function of IgG can swing from pro- to anti-inflammatory states with small changes in glycan structure at Asparagine-297 of IgG Fc domain. This variation is implicated in pathophysiology of autoimmune diseases such as rheumatoid arthritis. Although our understanding about the structure-function relation of IgG Fc glycosylation has immensely increased for the last four decades, it is still limited about the regulators of this glycan structure. To broaden our understanding, ex-vivo cell cultures derived from lymph node (LN), spleen (SP) and bone marrow (BM) of K/BxN mouse, which is a model for autoantibody-dependent rheumatoid arthritis, were established. The glycan structures of antigen purified anti-glucose-6-phosphate isomerase (anti-GPI) autoantibody heavy chains produced in these cultures were characterized using HPLC. According to the results, while IgG produced in LN is decorated with the highest amount of pro-inflammatory agalactosylated structure, IgG produced in SP has the highest amount of anti-inflammatory sialylated structure. Interestingly, IgG produced in BM stands in between them due to more balanced distribution of glycan structures. In conclusion, the ex-vivo cell cultures of LN, SP and BM were successfully established, and the contribution of IgG to on-going inflammation is regulated by the production site of anti-GPI autoantibody via glycan structures. In addition, N-glycan profile of anti-GPI autoantibody produced in LN closely replicates the N-glycan profile for anti-GPI autoantibody from K/BxN serum indicating that anti-GPI autoantibody in circulation is heavily produced in LN.
Keywords : Immunoglobuin G, IgG, Rheumatoid arthritis, Inflammation, Sialylation, Galactosylation, Pro-inflammatory, Anti-inflammatory, Glycosylation

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