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Publication : TOLL-like receptor ligands stimulate aberrant class switch recombination in early B cell precursors.

First Author  Edry E Year  2008
Journal  Int Immunol Volume  20
Issue  12 Pages  1575-85
PubMed ID  18974086 Mgi Jnum  J:143931
Mgi Id  MGI:3829348 Doi  10.1093/intimm/dxn117
Citation  Edry E, et al. (2008) TOLL-like receptor ligands stimulate aberrant class switch recombination in early B cell precursors. Int Immunol 20(12):1575-85
abstractText  TOLL-like receptor (TLR) ligands stimulate class switch recombination (CSR) in mature B cells. We showed earlier that developing B cells in the bone marrow (BM) express TLR9 and are responsive to CpG DNA. Since CSR is a critical process for synthesis of effector antibodies, we studied the competence of precursor B cells to undergo CSR in response to TLR ligands, and the regulation of these cells. We found that CSR is induced throughout B lymphopoiesis in response to CpG and to LPS. However, sequencing analysis revealed aberrant joining of the switch junctions. In addition, we found that this CSR is independent of IgM expression and/or VDJ assembly and is directed to a specific isotype by cytokines. Finally, we found that activation of the switched precursor B cells is regulated by Fas. Thus, BM B cells can be activated by TLR ligands to undergo CSR and to secrete non-IgM antibodies. However, the effector potential of these cells is regulated by the Fas pathway.
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