Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation

Abstract

Background: Activation of naive B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI (Cluster Assignment for Biological Inference), which identifies significant co-clustering of genes with similar Gene Ontology annotation. Results: CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Ligand-specific changes in the expression of other proton pump components and MHC class II, and the induction of receptor internalization/endocytosis provided experimental support for this hypothesis. Conclusions: The hypothesis that overrepresentation of vesicle transport genes in the BCR-specific gene cluster revealed by the CLASSIFI analysis of the gene expression microarray data reflected the activation of antigen processing and presentation pathways was validated experimentally. Furthermore, the CLASSIFI analysis has identified at least thirty-eight proteins as candidate components of the B cell antigen processing and presentation pathway.

Files

Additional details