Figure 1 |. Role of immune recognition pathways in antibody-mediated immunoselection of the microbiota.

a | Microbial products can differently influence the development of the antibody repertoire in the gut. This schematic shows how Toll-like receptor (TLR)- and MHC class II-mediated signalling influence T cell-independent and T cell-dependent antibody responses, respectively. T cell-independent antibody responses are promoted by the mitogenic activity of TLR engagement on B cells, and this leads to the generation of relatively low-affinity antibodies with polyreactive specificities. Peptide–MHC class II–T cell receptor (TCR) interactions place more stringent selection on maturing B cells, which reduces the overall diversity of antibody repertoires but results in the generation of high-affinity antibodies with high epitope specificity. b | Two models using species rank abundance curves predict the effect on the microbiota of differential immune signalling in T cell-independent and T cell-dependent antibody responses. The red lines in both panels represent the typical distribution of species in microbiota communities from the gut. A small subset of species numerically dominate the community, but most of the community diversity resides in the long-tailed distribution of rare species. Low-affinity polyreactive antibody repertoires are predicted to bind a wider array of species — that is, have greater antibody coverage of the total microbial community (blue dashed line in left panel) — whereas high-affinity monoreactive antibody repertoires are predicted to bind a more limited array of species — that is, have a narrower range of coverage of the total microbial community (blue dashed line in right panel). By focusing the antibody response against the most abundant species, T cell-dependent antibody responses should favour diversity by constraining the growth of the fastest replicators, which maintains niches for rare and more fastidious microbial species. DC, dendritic cell.