Repertoires of Antigen Receptors in Tdt Congenitally Deficient Mice

Abstract

Tdt deficient mice show lack of N region in V(D)J junctions of immunoglobulin and T cell receptor genes and revealed that “immature recombinase” in fetal stage would boil down to no more than a lack of Tdt. Although particular junctions which are thought to be created by homology-mediated joining are frequently observed, one fourth of junctions lacked even one bp of overlap, indicating the existence of a V(D)J joining pathway that is homology independent. Lymphocyte repertoire which express V_H81X gene without N region is negatively selected, which shows that the repertoire of Tdt deficient mice is not a truly fetal repertoire. Positive selection of thymocytes is more efficient in Tdt deficient mice. Furthermore Tdt^−/− mice produce significant amounts of anti-dsDNA antibodies as Tdt^+/+ mice, indicating that increased diversity of the third complementarity-determining region (CDR3) by Tdt is not essential for the expansion of precursor B cells programmed to produce anti-DNA antibodies.