Research Article: Terminal Deoxynucleotidyl Transferase (TdT) Inhibiti on of Cord Blood Derived B and T Cells Expansion

Date Published: June 30, 2017

Publisher: Tabriz University of Medical Sciences

Author(s): Sanaz Gholami, Seyede Momeneh Mohammadi, Aliakbar Movasaghpour Akbari, Ali Abedelahi, Alireza Alihemmati, Shirin Fallahi, Hojjatollah Nozad Charoudeh.

http://doi.org/10.15171/apb.2017.026

Abstract

Purpose: Terminal deoxynucleotidyl transferase(TdT) is a DNA polymerase that is present in immature pre-B and pre-T cells. TdT inserts N-nucleotides to the V (D) J gene segment during rearrangements of genes, therefore, it plays a vital role in the development and variation of the immune system in vertebrates. Here we evaluated the relationship between cytokines like interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) and TdT expression in cord blood mononuclear cells and also effect of inhibition in the expansion of B and T cells derived from cord blood.

Partial Text

Terminal deoxynucleotidyl transferase (TdT) is a nuclear enzyme in one unique parcel of the pol X family of DNA polymerase.1,2 In human, TdT activity is present in the immature fraction of thymocytes and bone marrow cells.3,4 TdT plays a vital role in the development and variation of the immune system in vertebrates.5-7 TdT contributes to the variation of antigen receptors by random addition of nucleotides to single-stranded DNA at the junctions recombination of immunoglobulin heavy-chain genes in B and T cells development.8-11

Terminal deoxynucleotidyl transferase (TdT) or terminal transferase as a DNA polymerase is expressed in pre B, pre T cells and in acute lymphoblastic leukemia (ALL) cells. recombination-activating genes (RAGs) and TdT are composite elements of V(D)J rearrangement.28 RAG-1 and RAG-2 proteins are present at breaks of double-strand at the border of recombination signal sequence (RSS, #250) and a coding segment during V(D)J rearrangements.29 T cell receptors (TCR) as an analogous to immunoglobulins as well as B cell receptor (BCR) are complex. The diversity of T and B cells receptors are ascribable to the junctional diversity generated during gene recombination.30,31 In BCR and TCR genes, TdT adds N-nucleotides to the V, D, and J exons during the gene rearrangements due to diversity and their important role in the evolution of immune cells.

All taken into consideration, it was found out that not only TdT expression increased by cytokines and TdT inhibition decreased B and T cells derived from cord blood, but also it altered the rate of proliferation and apoptosis.

The authors thank the Stem Cell Research Center, Tabriz University of Medical Sciences and also appreciate our colleagues in the Anatomical Science Department (Grant code: 5/104/624,research Ethical code: TBZMED.REC.1394.558).

Not applicable.

All authors declare complete responsibility of the content of the study with no conflict of interests.

 

Source:

http://doi.org/10.15171/apb.2017.026

 

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