The link between antibodies to OxLDL and natural protection against pneumococci depends on D(H) gene conservation.
J Exp Med
; 210(5): 875-90, 2013 May 06.
Article
em En
| MEDLINE
| ID: mdl-23589567
ABSTRACT
Selection and physiological production of protective natural antibodies (NAbs) have been associated with exposure to endogenous antigens. The extent to which this association depends on germline NAb sequence is uncertain. Here we show that alterations in germline D(H) sequence can sever the association between the production of self-reactive NAbs and NAbs that afford protection against a pathogen. In unmanipulated hosts, the availability of the evolutionarily conserved DFL16.1 gene segment sequence profoundly affected the serum levels of NAbs against bacterial phosphorylcholine but not oxidized low-density lipoprotein. Mice with partially altered DFL16.1 sequence could use N nucleotides to recreate the amino acid sequence associated with the classical protective T15 idiotypepositive NAbs, whereas those without DFL16.1 could not. DFL16.1 gene-deficient mice proved more susceptible to challenge with live Streptococcus pneumoniae. Our findings indicate that although production of self-reactive NAbs can be independent of germline D(H) sequence, their capacity to provide protection against pathogens cannot. The potential relevance of these findings for the rational design of vaccines is discussed.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções Pneumocócicas
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Streptococcus pneumoniae
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Cadeias Pesadas de Imunoglobulinas
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Sequência Conservada
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Lipoproteínas LDL
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Anticorpos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article