Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets

PLoS One. 2007 Sep 12;2(9):e863. doi: 10.1371/journal.pone.0000863.

Abstract

Background: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocyte Subsets
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Profiling
  • Immunologic Memory
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism
  • Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / metabolism
  • Toll-Like Receptors / genetics*

Substances

  • Toll-Like Receptors