Autoreactive B Cell Receptors Mimic Autonomous Pre-B Cell Receptor Signaling and Induce Proliferation of Early B Cells
| Autor: | Juliane Kofer, Hedda Wardemann, Cathrin Eschbach, Elias Hobeika, Sonja Meixlsperger, Eva Hug, Hassan Jumaa, Fabian Kohler |
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| Rok vydání: | 2008 |
| Předmět: |
Recombinant Fusion Proteins
Naive B cell B-cell receptor Immunology Receptors Antigen B-Cell Mice Transgenic Biology Autoantigens Cell Line Mice hemic and lymphatic diseases medicine Animals Immunology and Allergy MOLIMMUNO Receptor B cell Adaptor Proteins Signal Transducing B-Lymphocytes Molecular Mimicry breakpoint cluster region Cell biology B-1 cell DNA-Binding Proteins medicine.anatomical_structure Infectious Diseases Cell culture Pre-B Cell Receptors Signal transduction Signal Transduction |
| Zdroj: | Immunity. 29(6):912-921 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2008.10.013 |
| Popis: | SummaryThe 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 λ5 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. |
| Databáze: | OpenAIRE |
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