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Development of Human Peripheral TCRBJ Gene Repertoire¹

First Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Previous studies of TCRBJ gene repertoires of human peripheral T lymphocytes showed that all TCRBV family transcripts had some common features in BJ gene usage, and nevertheless, transcripts of each BV family gene had a distinct pattern. To discern how the development of the peripheral BJ repertoire is controlled, the effects of preferential BJ gene rearrangement, thymic selection, and peripheral stimulation on the repertoire formation were investigated. A PCR-ELISA technique was used to examine the immature CD3^-CD4⁺CD8^-, and mature CD3⁺CD4⁺CD8^- and CD3⁺CD4^-CD8⁺ thymocytes, and peripheral CD4⁺ and CD8⁺ T lymphocytes for their BJ gene repertoires. Analogous to the peripheral repertoire, the BJ gene repertoires of the immature thymocytes displayed common features, and each BV transcript had a distinct pattern. All features were conserved well by those of mature thymocytes and peripheral T lymphocytes. In addition, the BJ gene repertoires of mature CD4 and CD8 thymocytes and peripheral lymphocytes with the same coreceptors were apparently different in a few BV-BJ combinations. The results showed that the overall BJ gene repertoire pattern was developed before antigenic selection. Thus, the preferential BJ gene expression, primarily based on preferential use of certain BJ gene rearrangements, dictates the peripheral BJ gene repertoire, which is then further modified by thymic selection and peripheral stimulation.

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