The pre-B cell receptor: turning autoreactivity into self-defense.
The first step in establishing the antibody repertoire in humans and mice is the rearrangement of immunoglobulin heavy chain (HC) genes in early B lineage cells. These cells then assemble microHCs with surrogate light chains (SLC) into a pre-B cell receptor (pre-BCR). We propose that the pre-BCR has evolved from an ancient autoreactive BCR, since the SLC is an autoreactive entity that binds to the pre-BCR itself and to other self-antigens. Abrogation of autoreactivity in the SLC diminishes pre-BCR signaling and impairs the clonal expansion of pre-B cells producing functional microHCs. Since SLC expression is restricted to pre-B cells, the autoreactivity encoded by the pre-BCR can be utilized to pre-select the antibody repertoire, while simultaneously avoiding the formation of autoreactive B lymphocytes.
Vettermann
Christian
C
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Jäck
Hans-Martin
HM
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D054420:Pre-B Cell Receptors / Q000276:immunology* / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction
D001324:Autoantigens; D054420:Pre-B Cell Receptors