The Lymphochip: A Specialized cDNA Microarray for the Genomic-scale Analysis of Gene Expression in Normal and Malignant Lymphocytes

Immunologists have a long tradition of dissecting thecellular components of the immune system based on theexpression of cell surface markers. Because of the easewith which immune cell subsets can be identified andsorted using these markers, the immune system is one ofthe best-understood differentiation systems in mammalian biology. Despite this success, the known lymphoid subsets are defined by using only a handful of theapproximately 100,000 genes in the mammalian genome.Recently, methods have been developed that offer a genomic-scale analysis of gene expression, and we have begun to view the immune system from this new perspective. Two technical advances have enabled this genomicview of biology: high throughput sequencing of cDNA libraries for gene discovery (Adams et al. 1992) and microarray technology for genomic-scale quantitation ofgene expression (Schena et al. 1995, 1996; Lockhart et al.1996; Shalon et al. 1996). These two technologies are intimately coupled, since microarray technology can onlymeasure the expression of genes for which a sequenceand/or a physical clone exists. In this paper, we summarize our work combining these two methodologies to understand the gene expression program of normal B-lymphocyte differentiation and its relationship to the geneexpression profiles of human B-cell malignancies...