Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells

Innate Immun. 2016 Aug;22(6):433-43. doi: 10.1177/1753425916651985. Epub 2016 Jun 1.


Neonatal innate immunity is distinct from that of adults, which may contribute to increased susceptibility to infection and limit vaccine responses. B cells play critical roles in protection from infection and detect PAMPs via TLRs, that, when co-activated with CD40, can drive B-cell proliferation and Ab production. We characterized the expression of TLRs in circulating B cells from newborns and adults, and evaluated TLR- and CD40-mediated naïve B-cell class-switch recombination (CSR) and cytokine production. Gene expression levels of most TLRs was similar between newborn and adult B cells, except that newborn naïve B cells expressed more TLR9 than adult naïve B cells. Neonatal naïve B cells demonstrated impaired TLR2- and TLR7- but enhanced TLR9-mediated cytokine production. Significantly fewer newborn naïve B cells underwent CSR to produce IgG, an impairment also noted with IL-21 stimulation. Additionally, co-stimulation via CD40 and TLRs induced greater cytokine production in adult B cells. Thus, while newborn naïve B cells demonstrate adult-level expression of TLRs and CD40, the responses to stimulation of these receptors are distinct. Relatively high expression of TLR9 and impaired CD40-mediated Ig secretion contributes to distinct innate and adaptive immunity of human newborns and may inform novel approaches to early-life immunization.

Keywords: B lymphocyte; TLR; class-switch recombination; cytokine; neonatal.

MeSH terms

  • Adult
  • Animals
  • Antibody Formation*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • CD40 Antigens / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Enzyme-Linked Immunospot Assay
  • Humans
  • Immunity, Innate*
  • Immunoglobulin Class Switching
  • Immunologic Memory*
  • Infant, Newborn
  • Interleukins / metabolism
  • Lymphocyte Activation
  • Toll-Like Receptor 9 / metabolism


  • CD40 Antigens
  • Cytokines
  • Interleukins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • interleukin-21