Unravelling the Impact of Outer Membrane Protein, OmpA, From S. Typhimurium on Aberrant AID Expression and IgM to IgA Class Switching in Human B-Cells

Abstract

Salmonella enterica serovar Typhimurium is a Gram-negative bacterium that causes gastrointestinal infection and poses significant public health risks worldwide. This study aims to explore how S. Typhimurium manipulates B-cell function through outer membrane protein A (OmpA). We investigate the effect of OmpA on Raji human B-cells, leading to the induction of activation-induced cytidine deaminase (AID) protein, which plays an important role in generating antibody diversity in B-cells, via initiating the process of somatic hypermutation (SHM) and class switch recombination (CSR). Our key findings demonstrate that OmpA is crucial for inducing aberrant AID expression in B-cells, leading to increased CSR. Interestingly, the increased AID expression was likely due to overexpression of cMYC, an activator for AID expression. Not only was the expression of cMYC elevated, but its occupancy on the aicda locus was raised. Furthermore, increased AID expression induced CSR events, specifically switching to IgA. In summary, our study suggests that OmpA plays a potential role in modulating B-cell regulation and controlling the adaptive immune system. These functional attributes of OmpA implicate its potential as a therapeutic target for combating S. Typhimurium pathogenesis. © 2025 John Wiley & Sons Ltd.