Autoreactive B cell receptors mimic autonomous pre-B cell receptor signaling and induce proliferation of early B cells.
The majority of early immature B cells express autoreactive B cell receptors (BCRs) that are, according to the current view, negatively selected to avoid the production of self-reactive antibodies. Here, we show that polyreactive BCRs, which recognize multiple self-antigens, induced autonomous signaling and selective expansion of B cell precursors in a manner comparable to the pre-BCR. We found that the pre-BCR was capable of recognizing multiple self-antigens and that a signaling-deficient pre-BCR lacking the non-Ig region of the surrogate-light-chain component lambda5 was rescued by the complementarity-determining region 3 derived from heavy chains of polyreactive receptors. Importantly, bone marrow B cells from mice carrying Ig transgenes for an autoreactive BCR showed increased cell-cycle activity, which could not be detected in cells lacking the transgenic BCR. Together, the pre-BCR has evolved to ensure self-recognition because autoreactivity is required for positive selection of B cell precursors.
Köhler
Fabian
F
Department of Molecular Immunology, Faculty of Biology and Centre for Biological Signalling Studies (bioss), Albert-Ludwigs-University and Max-Planck-Institute for Immunobiology, 79108 Freiburg, Germany.
Hug
Eva
E
Eschbach
Cathrin
C
Meixlsperger
Sonja
S
Hobeika
Elias
E
Kofer
Juliane
J
Wardemann
Hedda
H
Jumaa
Hassan
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry / Q000235:genetics; D054420:Pre-B Cell Receptors / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C113939:B cell linker protein; D004268:DNA-Binding Proteins; D054420:Pre-B Cell Receptors; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins