Predominant Autoantibody Production by Early Human B Cell Precursors

TLDR

B‑cell development generates a diverse antibody repertoire through random gene segment reassortment, but this process can produce self‑reactive antibodies. The study quantified how often self‑reactive antibodies arise in human B cells and how they are regulated. 55–75 % of early immature B cells produce self‑reactive antibodies, which are largely eliminated at two developmental checkpoints; failure of these checkpoints would markedly raise circulating autoantibodies.

Abstract

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.