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Publication : Effect of a genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production by C57BL6 Fas(lpr) mice.

First Author  Molano ID Year  2000
Journal  Clin Immunol Volume  94
Issue  1 Pages  24-32
PubMed ID  10607487 Mgi Jnum  J:110248
Mgi Id  MGI:3639787 Doi  10.1006/clim.1999.4797
Citation  Molano ID, et al. (2000) Effect of a genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production by C57BL6 Fas(lpr) mice. Clin Immunol 94(1):24-32
abstractText  Terminal deoxynucleotidyl transferase (TdT) adds nontemplate coded nucleotides (N additions) between the recombining ends of immunoglobulin and T cell receptor genes. These nucleotides add significant diversity to the Ig and TCR repertoires. Amino acids coded for by these nucleotides play a key role in the binding of self antigens by autoantibodies and autoreactive T cells. To determine the effect of a lack of N additions on autoantibody production, we bred the TdT knockout genotype onto the autoimmune C57BL/6-Fas(lpr) background. TdT-deficient mice had significantly lower sera anti-DNA and rheumatoid factor activity than their TdT-producing littermates. C57BL/6-Fas(lpr) TdT-deficient mice had shorter VH CDR3 regions and fewer VH CDR3 arginines [0.6% versus 4. 7%] than their TdT-producing littermates. These data indicate that the absence of TdT limited the production of anti-DNA antibodies and rheumatoid factors in C57BL/6-Fas(lpr) mice, likely due to constraints on Ig diversity secondary to the lack of TdT-derived N additions.
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