Gene Expression Patterns in Human and Mouse B Cell Development

Abstract

B lymphocytes develop in the mammalian bone marrow through a series of developmental stages that can be ordered by recombination status of the immunoglobulin genes. Recent studies have combined RNA amplification by in vitro transcription with high-density oligonucleotide array technology to generate gene expression profiles of ex vivo isolated B cell precursor stages from humans and mice. Cellular differentiation through five subsequent stages of mouse B cell development involves differential expression of 10.7% of the 13,104 genes analysed, while between 2.8% and 6.8% change upon differentiation fromone stage to the next. Early precursors express primarily genes involved in general metabolic processes, while B cell-specific functions are acquired in more mature stages. In human B cell development, pre-BI and small pre-BII cells express genes necessary for interactions with the respective microenvironments,while cycling, large pre-BII cells have a more cell-autonomous expression pattern. A direct comparison between human and mouse B cell development is hampered by the limited number of homologues that can be identified by reciprocal basic local alignment search tool (BLAST) searches of non-redundant expressed sequence tags (EST) clusters or of the available genome sequences. However, genes for which homologues could be identified that are differentially expressed during B cell development of both human and mouse have very similar expression patterns in the two species, are often expressed in large pre-BII cells, and are involved in DNA replication and cell-cycle regulation. Many more genes with homologous sequences, however, are differentially expressed during B cell development of only one species, indicating that genes can be used in different functional contexts even when the sequence is conserved. This implies that care should be taken with the interpretation of gene expression data from model organisms.