TGF‐β1 impairs IgA class switch recombination and production in porcine Peyer's patches B cells

Abstract

AbstractSecretory IgA is crucial for preventing the invasion of entero‐pathogens via intestinal mucosa. While it is well‐established that Transforming growth factor β1 (TGF‐β1) regulates IgA production in human and mouse B cells, our previous investigation revealed different functions of TGF‐β1 in IgA generation in pigs compared with humans and mice, with the underlying mechanism remaining elusive. In this study, IgM+ B cells from porcine Peyer's patches (PPs) were isolated and stimulated with recombinant porcine TGF‐β1 to evaluate the effect of TGF‐β1 on pigs. The results showed that antibody production from B cells of PPs was impaired by TGF‐β1 ex vivo. Furthermore, TGF‐β1 treatment led to a decrease in the expression of germ‐line transcript αand postswitch transcript α. Moreover, we observed that TGF‐β1 predominantly inhibited the phosphorylation of p38‐mitogen‐activated protein kinases (MAPK), confirming the involvement of the p38‐MAPK pathway in porcine IgA generation and IgA class switch recombination. The application of p38‐MAPK inhibitor resulted in decreased B‐cell differentiation levels. Collectively, this study demonstrates that exogenous TGF‐β1 restrains the production and class switch recombination of IgA antibodies by inhibiting p38‐MAPK signaling in porcine PPs B cells, which may constitute a component of TGF‐β1‐mediated inhibition of B‐cell activation.