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The role of Terminal deoxynucleotidyl Transferase (TdT) in the T‐cell‐independent antibody response to α 1–3 Dextran
Author(s) -
Mahmoud Tamer I,
Kearney John F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.849.4
Subject(s) - clone (java method) , terminal deoxynucleotidyl transferase , microbiology and biotechnology , antibody , antigen , biology , b cell , biochemistry , immunology , dna , apoptosis , tunel assay
Understanding the antibody response to T‐cell independent (TI‐2) antigens, such as polysaccharides associated with many pathogenic microorganisms, is of importance for improving vaccine design. We sought to study the factors that influence the development of B cell clones that are specific for TI‐2 antigens. In this study, we investigated the role of the lymphoid specific enzyme TdT in generating B cell clones responsive to the polysaccharide α 1–3 Dextran (DEX). TdT is a DNA polymerase crucial for the diversity of antigen receptors during V(D)J recombination via its non‐templated nucleotide additions. By using idiotypic markers for the major B cell clone J558 involved in the anti‐DEX response, we show that TdT−/− mice have lower numbers of the J558 clone than wildtype (WT) mice. Likewise, the DEX‐specific antibody response is lower in TdT−/− mice than WT mice and J558 was not detected in the sera of TdT−/− mice. By sequencing antibody heavy chain V(D)Js of sorted plasma cells post‐immunization, we show that TdT−/− mice generate the alternative M104E clone that predominates in neonatal life rather than the predominant adult clone J558. WT sequences show diversity in only two amino acids at the D segment of the CDR3 region. These data suggest that TdT is essential for the generation of the higher affinity DEX‐responsive J558 clone. Supported by National Institutes of Health (AI007051‐31A1 to T.M. and AI045794‐09 to J.F.K.)