The vast majority of immunoglobulin (Ig)A production occurs in mucosal tissue following T-cell dependent and T-cell independent antigen responses. To study the nature of each of these responses, we analyzed the gene expression and Ig reactivity profiles of T-cell dependent CD27+IgA+ and T-cell independent CD27-IgA+ circulating memory B cells. Gene expression profiles of IgA+ subsets were highly similar to each other and to IgG+ memory B-cell subsets with typical upregulation of activation markers and downregulation of inhibitory receptors. However, we identified mucosa-associated CCR9 and RUNX2 genes specifically upregulated in CD27-IgA+ B cells. We also found that CD27-IgA+ B cells expressed antibodies with distinct Ig repertoire and reactivity than those from CD27+IgA+ B cells. Indeed, antibodies from CD27-IgA+ B cells were weakly mutated, often utilized the Igλ light chain and were enriched in polyreactive clones recognizing various bacterial species. Hence, T-cell independent IgA responses are likely involved in the maintenance of gut homeostasis through the production of polyreactive mutated IgA antibodies with crossreactive anti-commensal reactivity.