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Evidence That Terminal Deoxynucleotidyltransferase Expression Plays a Role in Ig Heavy Chain Gene Segment Utilization¹

Molecualar Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104

TdT is a nuclear enzyme that catalyzes the addition of random nucleotides at Ig and TCR V(D)J junctions. In this paper we analyze human IgH rearrangements generated from transgenic minilocus mice in the presence or absence of TdT. In the absence of TdT, the pseudo-V_H gene segment present in the minilocus is rearranged dramatically more frequently. Additionally, J_H6 gene segment utilization is increased as well as the number of rearrangements involving only V_H and J_H gene segments. Thus, the recombination of IgH gene segments that are flanked by 23-nt spacer recombination signal sequences may be influenced by TdT expression. Extensive analysis indicates that these changes are independent of antigenic selection and cannot be explained by homology-mediated recombination. Thus, the role played by TdT may be more extensive than previously thought.

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