SFB-Driven Remodeling of Peyer’s Patches Enhances IgA and IgG2b Class Switching and Atypical Memory B Cell Generation II

The intestinal microbiota plays a central role in shaping host mucosal immunity, but the mechanisms by which specific commensals influence B cell responses remain incompletely defined. Segmented filamentous bacteria (SFB), potent inducers of Th17 cells, have been implicated in both protective and pathogenic immune outcomes. Here, we show that SFB colonization in specific pathogen-free (SPF) mice induces a profound remodeling of Peyer’s patches (PPs), characterized by increased cellularity, germinal center (GC) formation, and robust class switching to IgA and IgG2b, but not IgG1. Using flow cytometry, bone marrow chimeras, and single-cell RNA sequencing coupled with BCR repertoire analysis, we demonstrate that SFB enhances recruitment of naïve B cells through the CXCR5-CXCL13 axis and promotes T cell-dependent expansion of both GC and memory B cells. These memory B cells exhibit hallmark features of atypical B cells (ABCs), including CD11c expression and somatic hypermutation, and arise via a GC-dependent pathway. SFB increases the number of activated CD11c+SIRPa+BST2-CD11b+ DCs in the the PP subepithelial dome (SED), and T helper 17 (Th17) and T follicular helper (Tfh) cells. Surprisingly, unlike previous reports, neither Th17 effector function (IL-17R-/-) nor Th17-to-Tfh conversion (CD4CRE-RORgtfl/fl) was essential for the observed B cell changes. Finally, we show that SFB colonization enhances clonal diversity and somatic hypermutation in IgA⁺ and IgG2b⁺ B cells qualitatively as well as quantitatively. These findings establish a mechanistic link between microbiota composition and mucosal B cell immunity, with implications for vaccine responses, mucosal homeostasis, and autoimmune susceptibility.