TLR-dependent anti-commensal antibodies regulate intestinal immune homeostasis (MUC9P.750)

Maternal antibodies have been suggested to be important for establishing intestinal immune homeostasis in developing offspring, yet the mechanisms by which maternal antibodies achieve this remain unclear. We analyzed the gut immune response in mice born to antibody-deficient dams and found that maternal antibodies regulate the activation of mucosal CD4+ T cells. Interestingly, maternal IgA, the dominant mucosal antibody isotype, was not necessary for this regulation. As such, we developed an unbiased flow cytometric based assay to assess the microbiota-specific antibody response, thereby allowing us to investigate if other antibody isotypes are important for enforcing intestinal immune homeostasis. Unexpectedly, we found that mice generate a robust anti-commensal IgG2b- and IgG3- response. This commensal-specific IgG response occurs through a pathway independent of T cells, yet dependent on signaling through TLR2 and TLR4. These TLR-dependent anti-commensal IgG antibodies are transmitted from mothers to their offspring. There, they function to regulate T follicular helper responses and subsequently dampen germinal center B cell responses. This work reveals a feedback loop whereby T cell-independent antibody responses function to regulate mucosal CD4+ T cell responses and thereby establish equilibrium between the host and its resident microbiota.