Censoring of autoreactive B cell development by the pre-B cell receptor

RA Keenan, A De Riva, B Corleis, L Hepburn… - Science, 2008 - science.org
RA Keenan, A De Riva, B Corleis, L Hepburn, S Licence, TH Winkler, IL Mårtensson
Science, 2008science.org
Antibody diversity occurs randomly as B cells recombine their immunoglobulin (Ig) heavy-
and light-chain genes during development. This process inevitably generates reactivity
against self structures, and several mechanisms prevent the development of autoreactive B
cells. We report here a role for the pre-B cell receptor, composed of Ig heavy and surrogate
light chains, in the negative selection of cells expressing Ig heavy chains with the potential to
generate autoantibodies. Surrogate light-chain–deficient (SLC–/–) mice harbored elevated …
Antibody diversity occurs randomly as B cells recombine their immunoglobulin (Ig) heavy- and light-chain genes during development. This process inevitably generates reactivity against self structures, and several mechanisms prevent the development of autoreactive B cells. We report here a role for the pre-B cell receptor, composed of Ig heavy and surrogate light chains, in the negative selection of cells expressing Ig heavy chains with the potential to generate autoantibodies. Surrogate light-chain–deficient (SLC–/–) mice harbored elevated levels of antinuclear antibodies (ANAs) in their serum and showed evidence of escape of pre-B cells expressing prototypic autoantibody heavy chains from negative selection, leading to mature autoantibody secreting CD21CD23 B cells in the periphery. Thus, the pre-B cell receptor appears to censor the development of certain autoantibody-secreting cells and may represent an important factor in multifactorial autoimmune diseases.
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