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BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.

Publication ,  Journal Article
Kuraoka, M; Snowden, PB; Nojima, T; Verkoczy, L; Haynes, BF; Kitamura, D; Kelsoe, G
Published in: Cell Reports
February 2017

Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88. The first checkpoint is significantly impaired in AID- or MyD88-deficient mice and in mice doubly heterozygous for AID and MyD88, suggesting interaction of these factors in central B cell tolerance. Moreover, administration of chloroquine, an inhibitor of endosomal acidification, results in a failure to remove autoreactive immature/T1 B cells in mice. We propose that a BCR/TLR pathway coordinately establishes central tolerance by hyper-activating AID in immature/T1 B cells that bind ligands for endosomal TLRs.

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Published In

Cell Reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

February 2017

Volume

18

Issue

7

Start / End Page

1627 / 1635

Related Subject Headings

  • Toll-Like Receptors
  • Signal Transduction
  • Receptors, Antigen, B-Cell
  • Precursor Cells, B-Lymphoid
  • Phospholipase D
  • Myeloid Differentiation Factor 88
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Ligands
 

Citation

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MLA
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Kuraoka, M., Snowden, P. B., Nojima, T., Verkoczy, L., Haynes, B. F., Kitamura, D., & Kelsoe, G. (2017). BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance. Cell Reports, 18(7), 1627–1635. https://doi.org/10.1016/j.celrep.2017.01.050
Kuraoka, Masayuki, Pilar B. Snowden, Takuya Nojima, Laurent Verkoczy, Barton F. Haynes, Daisuke Kitamura, and Garnett Kelsoe. “BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.Cell Reports 18, no. 7 (February 2017): 1627–35. https://doi.org/10.1016/j.celrep.2017.01.050.
Kuraoka M, Snowden PB, Nojima T, Verkoczy L, Haynes BF, Kitamura D, et al. BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance. Cell Reports. 2017 Feb;18(7):1627–35.
Kuraoka, Masayuki, et al. “BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.Cell Reports, vol. 18, no. 7, Feb. 2017, pp. 1627–35. Epmc, doi:10.1016/j.celrep.2017.01.050.
Kuraoka M, Snowden PB, Nojima T, Verkoczy L, Haynes BF, Kitamura D, Kelsoe G. BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance. Cell Reports. 2017 Feb;18(7):1627–1635.
Journal cover image

Published In

Cell Reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

February 2017

Volume

18

Issue

7

Start / End Page

1627 / 1635

Related Subject Headings

  • Toll-Like Receptors
  • Signal Transduction
  • Receptors, Antigen, B-Cell
  • Precursor Cells, B-Lymphoid
  • Phospholipase D
  • Myeloid Differentiation Factor 88
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Ligands