TCR SELECTION AND ALLELIC EXCLUSION IN RAG TRANSGENIC MICE THAT EXHIBIT ABNORMAL T-CELL LOCALIZATION IN LYMPH-NODES AND LYMPHATICS

RAG-1 and RAG-2 are developmentally regulated genes that are essential for V(D)J recombination and lymphocyte development. Expression of RAG I and RAG-2 by thymocytes is normally limited to cells that have not c ompleted selection. We have previously documented that persistent expr ession of the recombinase activating genes (RAG) in transgenic mice re sults in aberrant thymic development, altered lymphatic microanatomy, and a profound immunodeficiency. Here we further document the patholog ic changes found in TG.RAG-1,2 mice and examine the role of TCR recomb ination and positive and negative thymic selection, as well as allelic exclusion, in the etiology of the phenotype. We find that neither sel ection nor TCR allelic exclusion can be overcome by transgenic express ion RAG-I and RAG-2 under the control of an Ick promoter.