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

Lee, Jamie A. and Sinkovits, Robert F. and Mock, Dennis and Rab, Eva L. and Cai, Jennifer and Yang, Peng and Saunders, Brian and Hsueh, Robert C. and Choi, Sangdun and Subramaniam, Shankar and Scheuermann, Richard H. (2006) Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation. BMC Bioinformatics, 7 (237). pp. 1-48. ISSN 1471-2105. doi:10.1186/1471-2105-7-237.

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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.

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Additional Information:© 2006 Lee et al., licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Submission date 21 September 2005; Acceptance date 2 May 2006; Publication date 2 May 2006 Authors’ contributions: JL carried out the microarray clustering, CLASSIFI analysis and experimental validation, and drafted the manuscript. RSS and DM participated in the microarray analysis and CLASSIFI design and implementation. ER and RCH participated in experimental validation. JC and PY participated in implementing the CLASSIFI algorithm as a web-based application. BS and SS participated in the CLASSIFI design and implementation. SC participated in the microarray analysis. RHS conceived of the study and the CLASSIFI algorithm, participated in its design, coordinated the study and helped to draft the manuscript. All authors participated in critical review of the manuscript and give final approval for the submitted manuscript. Acknowledgements: We thank the Alliance for Cellular Signaling (AfCS) for providing materials, methods, and expertise in the development of this work. The following authors are members of the AfCS: RSS, DM, BS, RCH, SC, SS, and RHS.
Issue or Number:237
Record Number:CaltechAUTHORS:LEEbmcbioinf06
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ID Code:2893
Deposited By: Archive Administrator
Deposited On:05 May 2006
Last Modified:08 Nov 2021 19:51

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