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Published Online June 19, 2008
Science DOI: 10.1126/science.1157533

Reports

Submitted on March 10, 2008
Accepted on May 27, 2008

Censoring of Autoreactive B Cell Development by the Pre-B Cell Receptor

Rebecca A. Keenan 1, Alessandra De Riva 1, Björn Corleis 2, Lucy Hepburn 1, Steve Licence 1, Thomas H. Winkler 3, Inga-Lill Mårtensson 1*

1 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
2 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.; Department of Molecular Immunology, Faculty for Biology, University Freiburg, Stübeweg 51, 79108 Freiburg, Germany.
3 Hematopoiesis Unit, Nikolaus-Fiebiger-Center, 91054 Erlangen, Germany.

* To whom correspondence should be addressed.
Inga-Lill Mårtensson , E-mail: lill.martensson{at}bbsrc.ac.uk

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 CD21–CD23– 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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Science. ISSN 0036-8075 (print), 1095-9203 (online)