Predominant Autoantibody Production by Early Human B Cell Precursors
Hedda Wardemann,1
Sergey Yurasov,1,3
Anne Schaefer,1
James W. Young,4
Eric Meffre,1,5*
Michel C. Nussenzweig1,2*
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.
1 Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA.
2 Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.
3 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
4 Allogeneic Bone Marrow Transplant and Clinical Immunology Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
5 Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: meffree{at}hss.edu, nussen{at}mail.rockefeller.edu
