Predominant autoantibody production by early human B cell precursors

H Wardemann, S Yurasov, A Schaefer, JW Young… - Science, 2003 - science.org
H Wardemann, S Yurasov, A Schaefer, JW Young, E Meffre, MC Nussenzweig
Science, 2003science.org
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 …
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.
AAAS