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Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 13, 2010
V(D) J actividad de la recombinasa en un subconjunto de linfocitos B del centro germinal
1Department of Microbiology and Immunology and Program in Molecular and Cell Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Science (New York, N.Y.)
|October 10, 1997
Resumen
Las células B del centro germinal pueden volver a expresar los genes RAG1 y RAG2, lo que permite nuevas especificidades de anticuerpos a través de la recombinación V(D) J. Este proceso, particularmente en las células B de baja afinidad, permite saltos evolutivos mientras se mantiene la selección de antígenos.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- Las células B del centro germinal son cruciales para la inmunidad adaptativa y la maduración de anticuerpos.
- La recombinación de J es esencial para generar diversos receptores de antígenos en el desarrollo de los linfocitos.
- El papel de la recombinación V(D) J en el centro germinal maduro de las células B no se entiende completamente.
Objetivo del estudio:
- Investigar la reexpresión y actividad de los genes activadores de la recombinasa V(D) J (RAG1 y RAG2) en el centro germinal de las células B.
- Para determinar las consecuencias funcionales de la recombinación secundaria V(D) J en el compartimiento de células B del centro germinal.
- Para entender cómo este proceso impacta la maduración de la afinidad del anticuerpo y la evolución de las células B.
Principales métodos:
- Análisis de los reordenamientos de la cadena ligera y de la cadena pesada de la inmunoglobulina kappa VDJ en el centro germinal de las células B.
- Detección de productos intermedios de la recombinación V(D) J.
- Evaluación de la afinidad del anticuerpo y la especificidad del receptor en las células B activas por recombinación.
Principales resultados:
- Se observó la reexpresión de RAG1 y RAG2 en un subconjunto de células B del centro germinal.
- Los abundantes productos intermedios de la recombinación V(D) J indican una actividad renovada en el locus de la cadena ligera de la inmunoglobulina kappa.
- Una proporción significativa de estas células recombinantemente activas contenía reordenamientos de cadena pesada de VDJ que codificaban anticuerpos de baja afinidad o no funcionales.
- La recombinación secundaria V(D) J parece ser inducida por una disminución de la unión del antígeno al ligando.
Conclusiones:
- La recombinación secundaria V(D) J en los centros germinales permite alteraciones significativas en la especificidad de los receptores de las células B.
- Este proceso está restringido a las células B con anticuerpos de baja afinidad o no funcionales, probablemente aquellos que se eliminan de la reacción del centro germinal.
- Este mecanismo preserva una selección eficiente impulsada por antígenos mientras permite saltaciones evolutivas en la evolución somática de las células B.
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