Censoring of Autoreactive B Cell Development by the Pre-B Cell Receptor
Rebecca A. Keenan,1
Alessandra De Riva,1
Björn Corleis,1,2
Lucy Hepburn,1
Steve Licence,1
Thomas H. Winkler,3
Inga-Lill Mårtensson1*
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.
1 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
2 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. E-email: lill.martensson{at}bbsrc.ac.uk
