Abstract: The invention provides novel caspase recruitment domain 11 (CARD11), also known as CARMA-1, polypeptides, nucleic acids encoding them and methods for making and using them. In one aspect, the polypeptides of the invention have NFkB activating activity. The invention also provides non-human transgenic animals, e.g., mice, comprising the CARD11 nucleic acids of the invention. The invention also provides pharmaceutical compositions comprising a nucleic acid or polypeptide of the invention. Administration of a pharmaceutical composition of the invention to a subject is used to generate a toleragenic immunological environment in the subject. This can be used to tolerize the subject to an antigen. The invention also provides inbred mouse strains homozygous for a non-wild type CARD11 allele. This genotype results in mice having a phenotype comprising dermatitis, B cell defects and T cell defects.