Development of antibody diversity in single germinal centers: selective expansion of high-affinity variants.
Eur J Immunol
; 24(10): 2393-400, 1994 Oct.
Article
en En
| MEDLINE
| ID: mdl-7925566
In a T cell-dependent immune response the microenvironment of the germinal center plays a crucial role in the affinity maturation of the antigen-specific, immunoglobulins. In order to look at the development of antibody diversity we have isolated single germinal centers and sequenced light chains characteristic of 2-phenyl-oxazolone (phOx)-specific antibodies. Fourteen days after immunization we can demonstrate various stages of intraclonal diversity. There are germinal centers where B cells are practically unmutated, suggesting that in these cases a substantial clonal expansion has taken place prior to the activation of the hypermutation mechanism. In other germinal centers, sequences with a low number of randomly distributed somatic mutations were observed, indicating that these changes have been introduced recently and/or that they fail to generate high-affinity variants and hence provide no basis for affinity selection. Finally, germinal centers are found in which practically all sequences carry the amino acid substitutions characteristic of the high affinity phOx antibodies. In these latter cases the high-affinity variants have been preferentially expanded. We conclude that affinity selection is a process that operates right from the beginning of germinal center development. Those B cells with a relative high affinity for the antigen gain a proliferative advantage over other cells and will dominate the response and these are the cells which will be selected to differentiate into memory cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bazo
/
Linfocitos B
/
Diversidad de Anticuerpos
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
1994
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania