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

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...

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Bibliographic Details
Published in:International immunology 2008-12, Vol.20 (12), p.1575-1585
Main Authors: Edry, Efrat, Azulay-Debby, Hilla, Melamed, Doron
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
antibodies
Antibody Formation - drug effects
Antibody Formation - immunology
B cells
B-Lymphocyte Subsets - cytology
B-Lymphocyte Subsets - metabolism
B-Lymphocytes - cytology
B-Lymphocytes - metabolism
Cells, Cultured
fas Receptor - metabolism
gene rearrangement
hematopoiesis
Immunoglobulin Class Switching - drug effects
Immunoglobulin Class Switching - immunology
In Situ Hybridization, Fluorescence
Ligands
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Mice
Mice, Knockout
Mice, Transgenic
Oligodeoxyribonucleotides - pharmacology
Precursor Cells, B-Lymphoid - cytology
Precursor Cells, B-Lymphoid - metabolism
Receptors, Antigen, B-Cell - biosynthesis
Receptors, Antigen, B-Cell - genetics
Signal Transduction - drug effects
Signal Transduction - immunology
Toll-Like Receptor 9 - agonists
Toll-Like Receptor 9 - genetics
Toll-Like Receptor 9 - metabolism
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Description
Summary: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.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxn117