Requirement of a Wnt5A-Microbiota Axis in the Maintenance of Gut B Cell Repertoire and Protection from Infection

Abstract

We investigated the influence of a Wnt5A-gut microbiota axis on gut B cell repertoire and protection from infection, having previously demonstrated that Wnt5A in association with gut commensals help shape gut T cell repertoire. Accordingly, Wnt5A heterozygous mice, which express less than wild type level of Wnt5A, and their isolated Peyers patches (PP), were studied in comparison with the wild type counterparts. The percentages of IgM and IgA expressing B cells were quite similar in the PP of both sets of mice. However, the PP of the Wnt5A heterozygous mice harbored significantly higher than wild type levels of microbiota bound B cell secreted IgA (sIgA), indicating the prevalence of a microbial population therein, that is significantly altered from that of wild type. Additionally, the percentage of PP IgG1 expressing B cells was appreciably depressed in the Wnt5A heterozygous mice in comparison to wild type. Wnt5A heterozygous mice, furthermore, exhibited notably higher than the wild type levels of morbidity and mortality following infection with Salmonella enterica, a common gut pathogen. Difference in morbidity/mortality correlated with considerable disparity between the PP-B cell repertoires of the Salmonella infected Wnt5A heterozygous and wild type mice, the percentage of IgG1 expressing B1b cells in the PP of heterozygous mice remaining significantly low as compared to wild type. Overall, these results suggest that a gut Wnt5A-microbiota axis is intrinsically associated with the maintenance of gut B cell repertoire and protection from infection. ImportanceAlthough it is well accepted that B cells and microbiota are required for protection from infection and preservation of gut health, a lot remains unknown about how the optimum B cell repertoire and microbiota are maintained in the gut. The importance of this study lies in the fact that it unveils a potential role of a growth factor termed Wnt5A in the safeguarding of the gut B cell population and microbiota, thereby protecting the gut from the deleterious effect of infections by common pathogens. Documentation of the involvement of a Wnt5A-microbiota axis in the shaping of a protective gut B cell repertoire, furthermore, opens up new avenues of investigations for understanding gut disorders related to microbial dysbiosis and B cell homeostasis that till date, are considered incurable.