Commensal Bacteria Recognition by Human Fetal Naive B cells

Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn sera contains abundant autoantibodies, suggesting that B cell tolerance during gestation is incomplete. To investigate this apparent paradox, we tested the reactivity of over 500 antibodies cloned from single B cells from human fetal liver, bone marrow, and spleen. We found that incomplete B cell tolerance mechanisms in early human fetal life favored the accumulation of autoreactive and polyreactive B cells with restricted repertoires that also bound human gut commensal bacteria. Fetal self-reactivity thus drives the selection of potentially beneficial innate-like B cells that may facilitate the removal of apoptotic cells during development and shape gut microbiota colonization and assembly after birth.