A heterozygous S32I mutation in IκBα that causes EDID results in defective development of lymphoid organs and impaired B cell function (68.13)

Abstract Autosomal ectodermal dysplasia with immunodeficiency (EDID) is caused by mutations in the inhibitor of NFκB α (IκBα), which is phosphorylated and degraded in response to several immune signaling pathways. We generated a mouse model of EDID by replacing one IκBα allele with a non-phosphorylatable IκBα, which resulted in decreased NFκB signaling. These mice have dysmorphic hair and teeth, as well as decreased serum immunoglobulins, and a severe decrease in their specific antibody response to T-dependent and T-independent antigens. The mice lack lymph nodes (LNs) and Peyers patches (PPs), and have a disrupted splenic architecture, with no marginal zone and fail to develop germinal centers (GCs). T cell function is intact but B cell function is deficient in vitro. Rag2 bone marrow chimeras formed proper lymphoid organs and had normal cutaneous hapten sensitivity but did not produce specific antibodies. This mouse model shows that autosomal EDID results in failure to develop LNs and PPs, disorganized splenic architecture, failure to develop GGs and an intrinsic B cell defect.