| First Author | Pedersen GK | Year | 2016 |
| Journal | Front Immunol | Volume | 7 |
| Pages | 65 | PubMed ID | 26973645 |
| Mgi Jnum | J:240145 | Mgi Id | MGI:5882473 |
| Doi | 10.3389/fimmu.2016.00065 | Citation | Pedersen GK, et al. (2016) Heterozygous Mutation in IkappaBNS Leads to Reduced Levels of Natural IgM Antibodies and Impaired Responses to T-Independent Type 2 Antigens. Front Immunol 7:65 |
| abstractText | Mice deficient in central components of classical NF-kappaB 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 IkappaB protein IkappaBNS in humoral immunity. IkappaBNS-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-kappaB signaling. We analyzed mice heterozygous for the identified IkappaBNS 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 IkappaBNS mutation, the heterozygous mice had normal frequencies of B-1 and MZB cells. These results suggest that there is a requirement for IkappaBNS expression from two functional alleles for maintaining normal levels of circulating natural IgM antibodies and responses to TI-2 antigens. |
