Only a Minority of B Cells Make the Cut

B cells that produce antibodies against the body's own proteins and DNA are for the most part purged from the repertoire. They are either forced into a state of unresponsiveness or made to undergo a process of receptor editing. Wardemann et al. now determine that the number of the autoreactive B cells in the preselected repertoire is surprisingly large and can make up as many as three-fourths of the total. Predominantly, these cells bear antibody specificities that are skewed toward polyreactive and anti-DNA specificities, seen, for example, in lupus and some other autoimmune conditions. Thus, the generation of high B cell diversity comes at the cost of burdening the systems for repertoire selection with applicants who are mostly destined to fail the test. H. Wardemann, S. Yurasov, A. Schaefer, J. W. Young, E. Meffre, M. C. Nussenzweig, Predominant autoantibody production by early human B cell precursors. Science 301 , 1374-1377 (2003). [Abstract] [Full Text]