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

Gabriel K. Pederse, Monika Ádor, Julian M. Star, Sharesta Khoenkhoe, Carrie Arnold, Bruce Beutler, Gunilla B. Karlsson Hedestam

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 ethyl-N-nitrosourea 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.

Original languageEnglish (US)
Article number65
JournalFrontiers in Immunology
Volume7
Issue numberMAR
DOIs
StatePublished - Mar 1 2016

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T Independent Antigens
Antibody Formation
Immunoglobulin M
Mutation
B-Lymphocytes
Humoral Immunity
Mutagenesis
Immunization
Alleles
Phenotype
Antibodies

Keywords

  • B-1 cells
  • IκBNS
  • NF-κB
  • Nfkbid
  • Transitional B cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Heterozygous mutation in IκBNS leads to reduced levels of natural IgM antibodies and impaired responses to T-independent type 2 antigens. / Pederse, Gabriel K.; Ádor, Monika; Star, Julian M.; Khoenkhoe, Sharesta; Arnold, Carrie; Beutler, Bruce; Karlsson Hedestam, Gunilla B.

In: Frontiers in Immunology, Vol. 7, No. MAR, 65, 01.03.2016.

Research output: Contribution to journalArticle

Pederse, Gabriel K. ; Ádor, Monika ; Star, Julian M. ; Khoenkhoe, Sharesta ; Arnold, Carrie ; Beutler, Bruce ; Karlsson Hedestam, Gunilla B. / Heterozygous mutation in IκBNS leads to reduced levels of natural IgM antibodies and impaired responses to T-independent type 2 antigens. In: Frontiers in Immunology. 2016 ; Vol. 7, No. MAR.
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