Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition

• DOI: 10.1126/science.aay9733
• Publication Date: 2021-04-01T17:12:44Z
• Authors: Jeff W. Chen; Tyler A. Rice; Jason M. Bannock; Agata A. Bielecka; Juliet D. Strauss; Jason R. Catanzaro; Haowei Wang; Laurence C. Menard; Jennifer H. Anolik; Noah W. Palm; Eric Meffre
• Keywords: 0301 basic medicine; B-Lymphocytes; Bacteria; Autoimmunity; Autoantigens; Antibodies; Immunity, Innate; V(D)J Recombination; 3. Good health; 03 medical and health sciences; Fetus; Organ Specificity; Pregnancy; Humans; Female; Autoantibodies

Prenatal antibodies are polyreactive

Extensive immunoglobulin gene rearrangements allow humans to recognize a diversity of potential pathogens. This antibody repertoire is more restricted during early life to prevent the generation of autoreactive B cells, though tolerance does not appear to be complete. Chen et al. examined the reactivities of antibodies cloned from individual human fetal B cells residing in the liver, bone marrow, and spleen. They observed the accumulation of autoreactive and polyreactive B cells, which were frequently cross-reactive to commensals in the absence of any somatic hypermutation. The generation of these reactive B cells before they are ever exposed to microbes may promote later beneficial commensal- host interactions and/or augmented host defense during the first weeks of life.

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