Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies

E Meffre, A Schaefer, H Wardemann, P Wilson… - The Journal of …, 2004 - rupress.org
E Meffre, A Schaefer, H Wardemann, P Wilson, E Davis, MC Nussenzweig
The Journal of experimental medicine, 2004rupress.org
Human B cells that coexpress surrogate and conventional light chains (V-preB+ L+) show an
unusual heavy and light chain antibody repertoire that display evidence of receptor editing.
However, it is unclear whether V-preB+ L+ B cells have been silenced by receptor editing or
still express autoreactive antibodies. Here we report that 68% of the antibodies expressed
by V-preB+ L+ B cells are autoreactive. A majority of these autoantibodies are true
antinuclear antibodies (ANA), and 50% of the ANAs are also reactive with a diverse group of …
Human B cells that coexpress surrogate and conventional light chains (V-preB+L+) show an unusual heavy and light chain antibody repertoire that display evidence of receptor editing. However, it is unclear whether V-preB+L+ B cells have been silenced by receptor editing or still express autoreactive antibodies. Here we report that 68% of the antibodies expressed by V-preB+L+ B cells are autoreactive. A majority of these autoantibodies are true antinuclear antibodies (ANA), and 50% of the ANAs are also reactive with a diverse group of antigens that include dsDNA, ssDNA, immunoglobulin, insulin, and bacterial lipopolysaccharide. Such antibodies are rarely encountered among conventional B cells. We conclude that V-preB+L+ B cells are a unique subset of normal circulating human B cells that escape central tolerance mechanisms and express self-reactive antibodies including potentially harmful ANAs.
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