Journal
TRENDS IN IMMUNOLOGY
Volume 31, Issue 5, Pages 176-183Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2010.02.004
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Funding
- European Community (EU)
- Interdisciplinary Center for Clinical Research (IZKF) Erlangen
- Deutsche Forschungsgemeinschaft (DFG) [SFB466, GK592, FOR832 (JA968/4)]
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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 mu HCs 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 mu HCs. 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.
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