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Front Immunol. 2016 Mar 1;7:65. doi: 10.3389/fimmu.2016.00065. eCollection 2016.

Heterozygous Mutation in IκBNS Leads to Reduced Levels of Natural IgM Antibodies and Impaired Responses to T-Independent Type 2 Antigens.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden.
2
Department of Genetics, The Scripps Research Institute , La Jolla, CA , USA.
3
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center , Dallas, TX , USA.

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.

KEYWORDS:

B-1 cells; IκBNS; NF-κB; nfkbid; transitional B cells

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