Higher levels of B-cell mutation in the early germinal centres of an inefficient secondary antibody response to a variant influenza haemagglutinin.
Immunology
; 157(1): 86-91, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30768794
ABSTRACT
Designing improved vaccines against mutable viruses such as dengue and influenza would be helped by a better understanding of how the B-cell memory compartment responds to variant antigens. Towards this we have recently shown, after secondary immunization of mice with a widely variant dengue virus envelope protein with only 63% amino acid identity, that IgM+ memory B cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein. Here, further investigation of memory responses to variant proteins, using more closely related influenza virus haemagglutinins (HA) that were 82% identical, produced a variant-induced boost response in the GC dominated by highly mutated B cells that failed, not efficiently improving serum avidity even in the presence of extra adjuvant, and that was worse than a primary response. This supports a hypothesis that over a certain level of antigenic differences, cross-reactive memory B-cell populations have reduced competency for affinity maturation. Combined with our previous observations, these findings also provide new parameters of success and failure in antibody memory responses.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vacinas contra Influenza
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Linfócitos B
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Receptores de Antígenos de Linfócitos B
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Centro Germinativo
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Influenza Humana
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article