@article{Regulates:2719,
      recid = {2719},
      author = {Okoreeh, Michael K},
      title = {CXCR4 Regulates B Cell Receptor Editing},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2020-12},
      pages = {147},
      abstract = {During B lymphopoiesis, B cell progenitors progress  through alternating and mutually exclusive stages of clonal  expansion and immunoglobulin (Ig) gene rearrangements.  Great diversity is generated through the stochastic  recombination of Ig gene segments encoding heavy and light  chain variable domains. However, this commonly generates  autoreactivity. Previous studies have shown that receptor  editing is the predominant central tolerance mechanism for  self-reactive B cells in the bone marrow. Receptor editing  rescues autoreactive B cells from negative selection, by  inducing renewed light chain recombination first at Igk  then Igl loci. Reports have indicated the lambda-chain has  distinct physiochemical properties that are particularly  effective at quenching autoreactivity to DNA; yet,  molecular mechanism of receptor editing that lead to the  usage of the lambda-chain remain ill defined. Herein, we  elucidate transcriptional and epigenetic features of  receptor editing cells and show chemokine receptor CXCR4 is  essential for maintaining the editing state and  orchestrating Igl light recombination. Editing small pre-B  cells possess unique open chromatin regions enriched for  E2A and NF-kB, key regulators of Igl recombination and  receptor editing. These regions showed evidence of having  been acquired by partial differentiation into the immature  B cell stage. Transcriptionally, editing cells showed  upregulation of oxidative phosphorylation, DNA repair  mechanisms and CXCR4. CXCR4 deficiency in autoreactive B  cells showed a selective defect in Igl recombination and  tolerance induction, suggesting CXCR4 is necessary for the  differentiation of Igl+ B cells during receptor editing.},
      url = {http://knowledge.uchicago.edu/record/2719},
      doi = {https://doi.org/10.6082/uchicago.2719},
}