Transcriptomics

Dataset Information

34

Cell intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses


ABSTRACT: Endosomal Toll-like receptors (TLRs) play an important role in the etiology of systemic autoimmune diseases such as SLE, where DNA- and RNA-associated autoantigens activate autoreactive B cells through TLR9- and TLR7-dependent pathways, respectively. Nevertheless, TLR9-deficient autoimmune prone mice develop more severe clinical disease, while TLR7-deficient and TLR7/9-double deficient autoimmune-prone mice develop less severe disease. To determine whether the regulatory activity of TLR9 is B cell intrinsic, we have now directly compared the functional properties of autoantigen activated WT, TLR9-deficient and TLR7-deficient B cells, in an experimental system where proliferation depends on BCR/TLR co-engagement. In vitro, TLR9-deficient cells are less dependent on survival factors for a sustained proliferative response than either WT or TLR7-deficient cells. The TLR9-deficient cells also preferentially differentiate toward the plasma cell lineage, as indicated by expression of CD138, sustained expression of IRF4, and other molecular markers of plasma cells. In vivo, autoantigen-activated TLR9-deficient cells give rise to greater numbers of autoantibody producing cells. Our results identify distinct roles for TLR7 and TLR9 in the differentiation of autoreactive B cells that explain the capacity of TLR9 to limit, and TLR7 to promote, the clinical features of SLE. AM14 WT, Tlr7-/-, Tlr9-/- and Tlr7/9-/- B cells were stimulated with PL2-3 for 0, 6, 24, and 42 hours, for a total of 16 samples.

ORGANISM(S): Mus musculus  

SUBMITTER: Louis M. Staudt   

PROVIDER: E-GEOD-58756 | ArrayExpress| 2015-03-06

SECONDARY ACCESSION(S): GSE58756PRJNA253370

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Cell-intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses.

Nündel Kerstin K   Green Nathaniel M NM   Shaffer Arthur L AL   Moody Krishna L KL   Busto Patricia P   Eilat Dan D   Miyake Kensuke K   Oropallo Michael A MA   Cancro Michael P MP   Marshak-Rothstein Ann A  

Journal of immunology (Baltimore, Md. : 1950) 20150213 6


Endosomal TLRs play an important role in systemic autoimmune diseases, such as systemic erythematosus lupus, in which DNA- and RNA-associated autoantigens activate autoreactive B cells through TLR9- and TLR7-dependent pathways. Nevertheless, TLR9-deficient autoimmune-prone mice develop more severe clinical disease, whereas TLR7-deficient and TLR7/9-double deficient autoimmune-prone mice develop less severe disease. To determine whether the regulatory activity of TLR9 is B cell intrinsic, we dire  ...[more]

Similar Datasets

2008-10-23 | GSE13300 | GEO
2014-05-04 | E-GEOD-13300 | ArrayExpress
2012-03-27 | E-GEOD-6674 | ArrayExpress
2010-12-22 | BIOMD0000000290 | BioModels Database
2010-12-22 | BIOMD0000000289 | BioModels Database
2015-11-24 | E-GEOD-41825 | ArrayExpress
2014-06-10 | E-GEOD-27579 | ArrayExpress
2013-05-16 | E-MEXP-3881 | ArrayExpress
2014-06-03 | E-GEOD-48781 | ArrayExpress
2011-03-02 | GSE27579 | GEO