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Author Notes:

To whom correspondence should be addressed: Bali Pulendran E-mail: bpulend@rmy.emory.edu

Conceived and designed the experiments: BP MG.

Performed the experiments: MG.

Analyzed the data: BP MG.

Contributed reagents/materials/analysis tools: JJ.

Wrote the paper: BP MG.

We would like to thank Dr. Timothy Denning for help with isolation of peyer's patch B cells from the intestine and Troy Querec for help with data analysis.

We also thank Ms. Leena Thomas for help with the screening of transgenic mice.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported by National Institutes of Health Grants RO1 DK 57665-01, RO1 AI48638-01, RO1 AI056499-01, NO1 A150025, NO1-A1-50019 and U19AI057266 (to BP).

Toll-Like Receptor Expression and Responsiveness of Distinct Murine Splenic and Mucosal B-Cell Subsets

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Journal Title:

PLoS ONE

Volume:

Volume 2, Number 9

Publisher:

, Pages e863-e863

Type of Work:

Article | Final Publisher PDF

Abstract:

Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen associated molecular patterns and trigger innate immunity leading to initiation of adaptive immunity. TLR-mediated activation of dendritic cells (DCs) is known to be a critical event in the initiation of cellular and humoral immune responses. Recent work however suggests that B cells also express TLRs, and that they can be activated via TLR ligands. However, whether such B cell activation occurs only on memory B cells, or whether it can also occur on truly naïve B cells remains controversial. Furthermore, the expression and functional relevance of TLRs on distinct subsets of B cells, which are known to play differential roles in humoral responses is not known. Methodology/Principal Findings In this study, we investigated the expression pattern of different TLRs in distinct subsets of murine B cells (naïve, memory, follicular, marginal zone, B-1 and peyer's patch). In contrast to the reported restricted expression pattern of TLRs in human peripheral blood naïve B cells, murine splenic naïve B cells express a variety of TLRs with the exception of TLR5 and 8. Consistent with this relatively broad expression pattern, murine naive B cells proliferate and secrete antibody to a variety of TLR agonists in vitro, in the absence of B-cell receptor cross-linking. In addition, we observed subtle differences in the antibody secretion pattern of follicular, marginal zone, B-1 and peyer's patch B-cell subsets. Conclusions/Significance Thus various B cell subsets, including truly naïve B cells, express multiple TLRs, and signaling via such TLRs results in their robust proliferation and antibody secretion, even in the absence of dendritic cell activation, or T-cell help.

Copyright information:

Copyright Gururajan et al.

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