Terminal deoxynucleotidyl transferase expression during neonatal life alters D(H) reading frame usage and Ig-receptor-dependent selection of V regions.
J Immunol
; 161(12): 6657-63, 1998 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-9862694
ABSTRACT
During neonatal life, Ig diversity is limited in many respects. The absence of terminal deoxynucleotidyl transferase (TdT) expression with the consequent lack of nontemplated addition during the neonatal period, coupled with the predominant usage of a single D(H) reading frame (RF), leads to severe limitations of diversity in the CDR3 region of Ig heavy (H) chains. The neonatal Ig H chain repertoire is also characterized by restricted V(H) usage, with predominant expression of certain V(H) segments, such as V(H)81x, that are rarely evident during adult life. In this report, we examine the effect of enforced TdT expression on the neonatal repertoire of V(H)81xDJ(H) rearrangements. We find that TdT synthesis abrogates D(H) RF bias during the fetal/neonatal period through a Ig-receptor-independent mechanism. These findings suggest that D(H) RF bias during neonatal life is determined largely by homology-directed joining. We also find that TdT synthesis alters the selection of productively rearranged V(H)81xDJ(H) alleles in the neonatal spleen through a Ig-receptor-dependent mechanism. Analysis of predicted CDR3 amino acid sequences indicates that positive selection of V(H)81x-encoded H chains is correlated with the presence of a consensus sequence immediately adjacent to the V(H) segment. These data support the hypothesis that the CDR3 region is critical in determining the ability of V(H)81x-encoded H chains to form functional receptors that support positive selection of B lymphocytes. Together, our results demonstrate that TdT can indirectly influence the Ig repertoire by influencing both receptor-dependent and receptor-independent selection processes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Rearranjo Gênico da Cadeia delta dos Receptores de Antígenos dos Linfócitos T
/
Cadeias delta de Imunoglobulina
/
DNA Nucleotidilexotransferase
/
Sistema Imunitário
/
Diversidade de Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Canadá