The development of adaptive immunity and responses to foreign molecules and organisms relies on the highly regulated production of hundreds of proteins. B-cell maturation, from committed progenitors to terminally differentiated plasma cells, is a multistep process that requires the ordered expression of a large number of genes. We studied anti-IgM-stimulated Ramos cells to explore genome-wide expression patterns in differentiating human B-cells. cDNA microarrays were used to measure changes in transcript levels over several days. A large set of genes ( approximately 1,500) showed significantly altered expression at one or more time points. The expression profiles were used to construct gene clusters that were then characterized further with respect to the functions of the encoded proteins. Several groups of genes relevant to B-cells were analyzed in detail including early response genes and genes related to transcription, apoptosis and cell cycle regulation. Extensive bioinformatics analyses were conducted to identify the genes/proteins and to study functions and pathways involving B-cells. The results pave the way for understanding the development of humoral immunity, and provide new candidate genes and targets for research and drug development.