Skip to main content
Journal cover image

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 Rep
February 14, 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 14, 2017

Volume

18

Issue

7

Start / End Page

1627 / 1635

Location

United States

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

APA
Chicago
ICMJE
MLA
NLM
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 Rep, 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 Rep 18, no. 7 (February 14, 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 Rep. 2017 Feb 14;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 Rep, vol. 18, no. 7, Feb. 2017, pp. 1627–35. Pubmed, 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 Rep. 2017 Feb 14;18(7):1627–1635.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 14, 2017

Volume

18

Issue

7

Start / End Page

1627 / 1635

Location

United States

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