Segmented filamentous bacteria (SFB) drives enhanced T cell-dependent IgA and IgG2b responses in Peyer's patches

Abstract Peyer’s patches (PPs) are the major site for T-cell dependent IgA B-cell differentiation. Segmented filamentous bacteria (SFB) are commensal bacteria that preferentially colonize the ileum, mainly over PPs. SFB colonization of germ-free mice induces polyclonal IgA responses by unclear mechanisms. Using scmRNAseq and flow cytometry we found SFB colonization of SPF mice induced an increase in the size and overall cell number in PPs that includes enhanced numbers of naïve, follicular, and germinal center B-cells as well as Th 17 and Tfh cells. SFB colonization increased the numbers of IgA +and IgG2b +, but not IgG1 +B-cells in PPs. Enhanced class-switching to IgA and IgG2b was dependent on T-cells, CCR6, CD40-CD40L and DC-expression of MHCII, as well as to some degree on IL-6. An increased number of activated CD11c +SIRPa +BST2 −CD11b +DCs with CCR6 +Th17 of SFB +compared to SFB −mice suggests increased initiation of IgA class switching in the PP subepithelial dome (SED). SFB colonization increased the conversion of Th17 into Tfh cells, however unlike previous reports, SFB-colonized IL-17R −/−and CD4 CRE-RORg tfl/flmice indicated that neither IL-17, nor the enhanced Tfh conversion from Th17 cells is required for increased IgA and IgG2b responses. Finally, B cell repertoire analysis from IgA +, IgG1 +and IgG2b +PP B cells showed SFB colonization affected the B-cell repertoire qualitatively as well as quantitatively. Together, these data indicate that SFB colonization enhances the recruitment of naïve B cells, as well as drives IgA and IgG2b antibody responses through enhanced T cell-dependent class switching in PPs, and contribute to our understanding of how commensal microbes affect humoral immune responses to infection and vaccination. This work was supported by the Division of Intramural Research, NIAID, NIH