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

Activation of naïve 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 proliferati...

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Published in:	BMC bioinformatics Vol. 7; no. 1; p. 237
Main Authors:	Lee, Jamie A, Sinkovits, Robert S, Mock, Dennis, Rab, Eva L, Cai, Jennifer, Yang, Peng, Saunders, Brian, Hsueh, Robert C, Choi, Sangdun, Subramaniam, Shankar, Scheuermann, Richard H
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 02-05-2006 BioMed Central BMC
Subjects:	Algorithms Antigen Presentation - physiology Antigens - metabolism B-Lymphocytes - metabolism Cells, Cultured Data Interpretation, Statistical Gene Expression Profiling - methods Humans Lymphocyte Activation - physiology Oligonucleotide Array Sequence Analysis - methods Protein Interaction Mapping - methods Receptors, Antigen, B-Cell - metabolism Signal Transduction - physiology Software
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Summary:	Activation of naïve 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. 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. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated. These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2105 1471-2105
DOI:	10.1186/1471-2105-7-237