Most self-reactive antibodies (green) are filtered from the developing immune system.


Waste is rife in the immune system, based on a report from Hedda Wardemann, Michel Nussenzweig (Rockefeller University, New York, NY), and colleagues. The group has determined that more than half of the human B cell antibody population is removed before maturation.

The removal is a consequence of antibody gene rearrangement—a random process that is certain to generate some autoreactive antibodies. Nussenzweig's group now shows just how often autoreactivity occurs by identifying autoreactive B cells at different stages of development. Between 55% and 75% of the antibodies made by early immature B cells react against self antigens. These potentially dangerous antibodies are removed from the repertoire at two checkpoints: the number of self-reactive antibody-producing B cells were halved from within the bone marrow and then halved again after entering the blood stream. Also, nearly 90% of developing B cells producing polyreactive antibodies, whose promiscuity is probably a risk to the host, were removed at the marrow checkpoint.These studies will help determine how autoimmune diseases arise. “Any problem in the checkpoints that would allow self-reactive B cells to get through might be dangerous,” says Wardemann. “We determined the numbers in normal, healthly donors. If we compare this to autoimmune patients, we should get an idea of where the problem lies.” ▪


Wardemann, H., et al. 2003. Science. 10.1126/science.1086907.