TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses

J Immunol. 2017 Jan 15;198(2):699-707. doi: 10.4049/jimmunol.1601335. Epub 2016 Dec 12.

Abstract

Toll-like receptors play a central role in the initiation of adaptive immune responses with several TLR agonists acting as known B cell mitogens. Despite thousands of publications on TLRs, the function of TLR10 remains unknown. We have found that Ab-mediated engagement of TLR10 on primary human B cells suppresses B cell proliferation, cytokine production, and signal transduction. When challenged with either a T independent or T dependent Ag, TLR10 transgenic mice exhibit diminished Ab responses. Adoptive transfer of splenic B cells into B cell-deficient mice revealed that the suppressive effects on Ag-specific humoral immune responses are entirely B cell intrinsic. Our results demonstrate that TLR10 has a functional role within the B cell lineage that is distinct from that of other TLR family members and may provide a potential therapeutic target for diseases characterized by dysregulated B cell activity.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • B-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Knock-In Techniques
  • Humans
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 10 / immunology*

Substances

  • Toll-Like Receptor 10