Frontiers in Immunology (Mar 2016)

Heterozygous mutation in IκBNS leads to reduced levels of natural IgM antibodies and impaired responses to T-independent type 2 antigens

  • Gabriel Karlsson Pedersen,
  • Monika eÁdori,
  • julian M Stark,
  • Sharesta eKhoenkhoen,
  • Carrie eArnold,
  • Bruce eBeutler,
  • Gunilla B Karlsson Hedestam

DOI
https://doi.org/10.3389/fimmu.2016.00065
Journal volume & issue
Vol. 7

Abstract

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Mice deficient in central components of classical NF-κB signaling have low levels of circulating natural IgM antibodies and fail to respond to immunization with T-independent type 2 (TI-2) antigens. A plausible explanation for these defects is the severely reduced numbers of B-1 and marginal zone B (MZB) cells in such mice. By using an ENU mutagenesis screen, we identified a role for the atypical IκB protein IκBNS in humoral immunity. IκBNS deficient mice lack B-1 cells and have severely reduced numbers of MZB cells and thus resemble several other strains with defects in classical NF-κB signaling. We analyzed mice heterozygous for the identified IκBNS mutation and demonstrate that these mice have an intermediary phenotype in terms of levels of circulating IgM antibodies and responses to TI-2 antigens. However, in contrast to mice that are homozygous for the IκBNS mutation, the heterozygous mice had normal frequencies of B-1 and MZB cells. These results suggest that there is a requirement for IκBNS expression from two functional alleles for maintaining normal levels of circulating natural IgM antibodies and responses to TI-2 antigens.

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