Preliminary analysis of spatial-temporal homogeneity and heterogeneity of TCR β chain CDR3 repertoires in BALB/c mice.

Abstract

The T-cell response and tolerance in non-lymph tissues differs from those in lymph tissues such as the spleen and thymus. The distribution and composition of the TCR repertoires in non-lymph tissues and how they differ and associate with their counterparts in lymph tissue remain unclear. Thus, we studied the thymus, spleen, blood, liver and small intestine of BALB/c mice at the ages of one, three and five months to carry out a preliminary analysis of the spatial-temporal homogeneity and heterogeneity of the total TCR β chain CDR3 repertoire using high-throughput sequencing technology and immune bioinformatics approaches. The data show that the diversity of the CDR3 repertoires was decreased as the mouse age increased, except in the small intestine. The number of low-expanded clones in the CDR3 repertoires was greatest in the thymus, followed by the spleen, blood, liver and small intestine, and highly expanded clones had an opposite trend in the different mice ages. The thymus and the spleen showed the greatest overlap of CDR3 sequences with the other tissues across the different mice ages. The distribution of the CDR3 repertoire length was normal, with a median of 14 aa in all the mouse tissues, except the small intestine of the one-month-old mice had a median of 12 aa. In summary, the composition and characteristics of the CDR3 repertoires in the thymus were similar to those in the spleen, and repertoires in the blood were similar to those in the liver; only the small intestine showed a unique composition. These results offer a novel method to explore the source, differentiation, proliferation and response of distinct T cells in different tissues at different mice ages.