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La selección clonal en el centro germinal por la proliferación regulada y la hipermutación

Alexander D Gitlin¹, Ziv Shulman¹, Michel C Nussenzweig²

¹Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.

|May 9, 2014

Resumen

Las células B en los centros germinales (GCs) se expanden y diversifican los genes de inmunoglobulina. La división celular y la hipermutación están reguladas por la captura y presentación de antígenos, lo que garantiza una selección de células B de alta afinidad.

Área de la Ciencia:

Inmunología Inmunología.
Biología Molecular Biología Molecular
Biología celular Biología celular.

Sus antecedentes:

Los linfocitos B experimentan expansión clonal y diversificación de genes de inmunoglobulina en los centros germinales (GC) durante las respuestas inmunes.
Las células B de alta afinidad se seleccionan a través de ciclos iterativos de división, hipermutación y selección en las zonas oscuras y claras de la GC.

Objetivo del estudio:

Investigar la regulación de la expansión clonal y la hipermutación durante los ciclos del centro germinal interzonal.
Para determinar si la extensión de la división celular y la hipermutación son proporcionales a la captura y presentación del antígeno.

Principales métodos:

Utilizó una estrategia transgénica para cuantificar la división celular dentro de los centros germinales.
Empleó un reportero fluorescente fotoactivado para examinar las tasas de hipermutación.
Combinó estos métodos para estudiar la dinámica de las células B en centros germinales.

Principales resultados:

Se encontró que tanto la división celular como la hipermutación son directamente proporcionales a la cantidad de antígeno capturado y presentado por las células GC B.
Demostrado que la presentación de antígenos a las células T auxiliares foliculares en la zona de luz es un paso regulador clave.
Se mostró una correlación directa entre la carga de antígenos y el grado de expansión y diversificación de las células B.

Conclusiones:

La extensión de la expansión clonal de las células B y la hipermutación del gen de inmunoglobulina en los centros germinales está regulada por el antígeno.
La captura y presentación de antígenos por las células GC B a las células T auxiliares foliculares controla la división y diversificación de las células B.
Este mecanismo asegura la expansión y diversificación selectiva de las células B de alta afinidad durante las respuestas inmunes.

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