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International Immunology Advance Access originally published online on October 29, 2008
International Immunology 2008 20(12):1575-1585; doi:10.1093/intimm/dxn117
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Efrat Edry1, Hilla Azulay-Debby1 and Doron Melamed1,2

1 Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 31096, Israel
2 Rappaport Family Institute for Research in the Medical Sciences, Technion—Israel Institute of Technology, Haifa, Israel

Correspondence to: D. Melamed; E-mail: melamedd{at}tx.technion.ac.il

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.

Keywords: antibodies, B cells, gene rearrangement, hematopoiesis

Transmitting editor: I. Pecht

Received 11 June 2008, accepted 26 September 2008.


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