Immune deficiency due to high copy numbers of an A_β^k transgene

Because allelic polymorphism of the major histocompatibility complex class II antigens affects the immune response at several levels, we wished to characterize the contribution of a particular α or β chain in vivo using transgenic mice. We have established and characterized 12 lines of H-2^s/s mice carrying from 1 to 65 copies of an A_β^k transgene. The transgene was coexpressed with the endogenous allele in a tissue-specific manner, and A_β^k mRNA expression correlated well with transgene copy number. High copy number (extreme overexpression) of the transgene was associated with a variety of defects, including a significant reduction in Ia cell-surface expression, a severe decrease in B-cell number, abnormal extramedullary granulopoiesis, and an increased susceptibility to infection. In this paper we describe in detail the phenotype associated with high copy numbers of the A_β^k transgene. The defects we have observed may be relevant to similar phenomena seen in other transgenic mice. In addition, these mice have fortuitously provided a system in which to assess the effect of various levels of class II cell-surface expression in the thymus on selection of the T-cell repertoire.