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Autoantibodies in mice lacking terminal deoxynucleotidyl transferase: evidence for a role of N region addition in the polyreactivity and in the affinities of anti-DNA antibodies.

S Weller, C Conde, A M Knapp, H Levallois, S Gilfillan, J L Pasquali and T Martin
J Immunol October 15, 1997, 159 (8) 3890-3898;
S Weller
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C Conde
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A M Knapp
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H Levallois
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S Gilfillan
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J L Pasquali
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T Martin
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Abstract

The generation of terminal deoxynucleotidyl transferase knockout mice (TdT0) has demonstrated that TdT is the only major activity involved in N region addition. This enzyme generates diversity by adding random nucleotides at the V-D-J junctions and by disrupting the formation of repetitive "homology-directed" junctions. Several studies have demonstrated that the Ig heavy chain third complementarity-determining region (H-CDR3) and the N region play a critical role: 1) in distinguishing between polyreactive and monospecific combining sites in natural and Ag-induced Abs; and 2) in the specificity and polyreactivity of natural autoantibodies (autoAbs) and in particular of anti-DNA Abs. To examine the impact of the lack of TdT on the natural autoAb repertoire in adult mice, we have stimulated TdT0 and TdT+ littermates with LPS. Serum studies demonstrate that TdT is not critical for the generation of B cells expressing autoAbs including anti-DNA Abs and rheumatoid factors. However, the generation of a large collection of hybridomas indicates that the frequencies of these cells are reduced in TdT0 mice mainly due to a lower incidence of polyreactivity; also, the lack of N region diversity seems to negatively affect the affinity of anti-DNA Abs. The physiologic relevance of these data is discussed.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 159, Issue 8
15 Oct 1997
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Autoantibodies in mice lacking terminal deoxynucleotidyl transferase: evidence for a role of N region addition in the polyreactivity and in the affinities of anti-DNA antibodies.
S Weller, C Conde, A M Knapp, H Levallois, S Gilfillan, J L Pasquali, T Martin
The Journal of Immunology October 15, 1997, 159 (8) 3890-3898;

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Autoantibodies in mice lacking terminal deoxynucleotidyl transferase: evidence for a role of N region addition in the polyreactivity and in the affinities of anti-DNA antibodies.
S Weller, C Conde, A M Knapp, H Levallois, S Gilfillan, J L Pasquali, T Martin
The Journal of Immunology October 15, 1997, 159 (8) 3890-3898;
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Print ISSN 0022-1767        Online ISSN 1550-6606