Bob1+ T follicular helper cells support intestinal mucosal immunity

Introduction The intestinal environment relies on immunoglobulin A (IgA) produced in mucosa-associated lymphoid tissues, including Peyer’s patches (PPs). While T follicular helper (Tfh) cells are known to facilitate germinal center (GC) formation in PPs, the mechanisms through which Tfh cells regulate IgA production remain unclear. B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator that interacts with octamer-binding transcription factors 1 and 2 (Oct1/2), is notably expressed in Tfh cells and regulates their function during persistent foreign antigen exposure. Methods To explore the role of Bob1 in Tfh cells and intestinal immunity, we studied T cell-specific Bob1-deficient mice (CD4 Cre/+ Bob1 fl/fl , FoxP3 GFP/DTR CD4 Cre/+ Bob1 fl/fl ) alongside control mice (CD4 +/+ Bob1 fl/fl , FoxP3 GFP/DTR CD4 +/+ Bob1 fl/fl ) under steady-state conditions. We assessed differences in IgA production and subsequently analyzed T and B cell subsets involved in IgA production within the lamina propria (LP) and PPs. Additionally, we examined changes in the intestinal microbial composition in both groups. Results Fecal IgA levels and the population of IgA + plasma cells in the small intestinal LP were significantly lower in CD4 Cre/+ Bob1 fl/fl mice than in control CD4 +/+ Bob1 fl/fl mice. Similarly, IgA + light zone GC B and IgA + memory B cells were found in reduced populations in PPs of CD4 Cre/+ Bob1 fl/fl mice compared with those in the controls. Furthermore, inducible T-cell costimulator expression was diminished in GC Tfh cells of FoxP3 GFP/DTR CD4 Cre/+ Bob1 fl/fl mice compared with that in controls. Analysis of the intestinal microbiota also revealed a reduced abundance of Bacteroidales-associated bacterial populations, including the family Prevotellaceae and Rikenellaceae, in CD4 Cre/+ Bob1 fl/fl mice. Conclusion Our findings indicate that Bob1 is crucial for Tfh cell activation in PPs, which in turn supports intestinal IgA responses and the maintenance of Bacteroidales-associated microbial communities. This study enhances our understanding of the mechanisms underlying intestinal immune responses and lays the groundwork for future research aimed at modulating mucosal immunity.