Molecular definition of the germinal centre stage of B–cell differentiation

Abstract

Genomic–scale gene expression analysis provides views of biological processes as a whole that are difficult to obtain using traditional single–gene experimental approaches. In the case of differentiating systems, gene expression profiling can define a stage of differentiation by the characteristic expression of hundreds of genes. Using specialized DNA microarrays termed ‘Lymphochips’, gene expression during mature B–cell differentiation has been defined. Germinal centre B cells represent a stage of differentiation that can be defined by a gene expression signature that is not shared by other highly proliferative B–cell populations such as mitogenically activated peripheral blood B cells. The germinal centre gene expression signature is maintained to a significant degree in lymphoma cell lines derived from this stage of differentiation, demonstrating that this gene expression programme does not require ongoing interactions with other germinal centre cell types. Analysis of representative cDNA libraries prepared from resting and activated peripheral blood B cells, germinal centre centroblasts, centrocytes and tonsillar memory B cells has confirmed and extended the results of DNA microarray gene expression analysis.