IMMUNOLOGICAL DEFECTS IN MICE WITH A TARGETED DISRUPTION IN BCL-3

The proto-oncogene bcl-3 is a member of the I kappa B family. The Bcl- 3 protein is known to interact specifically With the p50 and p52 subun its of NF kappa B. However, the function of this interaction is not we ll understood. To determine the in vivo role of Bcl-3, mice were gener ated that lack the bcl-3 gene, Eel 3(-/-). Here we report that Eel 3(- /-) mice appear developmentally normal, but exhibit severe defects in humoral immune responses and protection from in vivo pathogenic challe nges. Relative to wild-type mice, Eel 3(-/-) mice are unable to clear L. monocytogenes and are more susceptible to infection with S. pneumon iae. This phenotype is similar to that observed in the p50(-/-) mice a nd the cross between the Bcl-3(-/-) and p50(-/-) mice generates animal s with an enhanced phenotype. In accordance with the observed defects in their immune response, the Eel 3(-/-) mice have normal immunoglobul in levels before and after immunization, but fail to produce antigen-s pecific antibodies. Additionally, spleens from Bcl-3(-/-) mice are abn ormal and void of germinal centers. In contrast, the p50(-/-) mice hav e normal germinal centers. We propose that in in vivo, Bcl-3 can funct ion independently of p50.