Potent induction of antibody-secreting B cells by human dermal-derived CD14+ dendritic cells triggered by dual TLR ligation Academic Article uri icon

Overview

MeSH Major

  • Antibody-Producing Cells
  • Antigens, CD14
  • B-Lymphocyte Subsets
  • Cell Differentiation
  • Dendritic Cells
  • Dermis
  • Lymphocyte Activation
  • Toll-Like Receptors

abstract

  • Targeting CD14(+) dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naive B cells. In this study, we show that CD14(+) DDCs express mRNA for TLRs 1-9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14(+) DDCs, as shown by enhanced expression of B cell stimulatory cytokines (IL-6, IL-10, and TNF-α) and more pronounced phenotypic maturation. These combinations were resiquimod (R-848) plus polyinosinic-polycytidylic acid [Poly(I:C)], R-848 plus LPS, Pam3CSK4 plus Poly(I:C), and LPS plus Poly(I:C). We also found that selected TLR ligand pairs [R-848 plus either LPS or Poly(I:C)] were superior to individual agents at boosting the inherent capacity of CD14(+) DDCs to induce naive B cells to proliferate and differentiate into CD27(+) CD38(+) B cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14(+) DDCs also promoted the differentiation of Th1 (IFN-γ-secreting) CD4(+) T cells, but not of Th2 or Th17 CD4(+) T cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1.

publication date

  • December 15, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3951118

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1200601

PubMed ID

  • 23162132

Additional Document Info

start page

  • 5729

end page

  • 44

volume

  • 189

number

  • 12