Imbalanced IgA-IgG class switching recombination: a novel mechanism of gut immune dysregulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with significant disease burden that markedly impairs patients' quality of life. The pathogenesis of IBD is closely associated with hyperactive immunopathological responses. Emerging evidence has established humoral immunity as a crucial contributor to IBD development. Class switch recombination (CSR), the critical process enabling B cells to produce different antibody isotypes, plays a pivotal role in humoral immunity. While healthy intestinal mucosa predominantly contains immunoglobulin A (IgA) that maintains gut homeostasis, immunoglobulin G (IgG) becomes the dominant isotype during IBD and drives chronic inflammation. Therefore, understanding the signals and mechanisms governing antibody CSR may provide deeper insights into IBD pathogenesis. Herein, we review B cell activation pathways, the distinct roles of IgA and IgG in intestinal immunity, CSR-regulating signals, and recent discoveries in the context of IBD, with the aim of identifying novel therapeutic opportunities.