Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies.
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.
Meffre
Eric
E
Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA. meffree@hss.edu
Schaefer
Anne
A
Wardemann
Hedda
H
Wilson
Patrick
P
Davis
Eric
E
Nussenzweig
Michel C
MC
D000595:Amino Acid Sequence; D000917:Antibody Formation; D001323:Autoantibodies / Q000737:chemistry / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data
D001323:Autoantibodies; D000939:Epitopes; D007147:Immunoglobulin Light Chains