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J Immunol. 2013 Aug 1;191(3):1082-90. doi: 10.4049/jimmunol.1201569. Epub 2013 Jul 1.

Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen.

Author information

1
Program on Inflammatory Diseases, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.

Abstract

In the secondary lymphoid organs, intimate contact with follicular dendritic cells (FDCs) is required for B cell retention and Ag-driven selection during the germinal center response. However, selection of self-reactive B cells by Ag on FDCs has not been addressed. To this end, we generated a mouse model to conditionally express a membrane-bound self-antigen on FDCs and to monitor the fate of developing self-reactive B cells. In this article, we show that self-antigen displayed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage. Notwithstanding, some self-reactive B cells persist beyond this checkpoint, showing evidence of Ag experience and intact proximal BCR signaling, but they are short-lived and unable to elicit T cell help. These results implicate FDCs as an important component of peripheral B cell tolerance that prevents the emergence of naive B cells capable of responding to sequestered self-antigens.

PMID:
23817432
PMCID:
PMC3766769
DOI:
10.4049/jimmunol.1201569
[Indexed for MEDLINE]
Free PMC Article

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