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

• Published in: Frontiers in immunology 2016-03, Vol.7, p.65-65
• Main Authors: Pedersen, Gabriel K, Ádori, Monika, Stark, Julian M, Khoenkhoen, Sharesta, Arnold, Carrie, Beutler, Bruce, Karlsson Hedestam, Gunilla B
• Format: Article
• Language: English
• Subjects: B-1 cells; Immunology; IκBNS; Medicin och hälsovetenskap; NF-κB; Nfkbid; transitional B cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2016.00065

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.