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Vol. 12, Issue 1, 98-111, January 2002

LETTER
Changes in Gene Expression Profiles in Developing B Cells of Murine Bone Marrow

Reinhard Hoffmann,1,3,4 Thomas Seidl,1 Martin Neeb,2 Antonius Rolink,1 and Fritz Melchers1,4

1 Basel Institute for Immunology, 4005 Basel, Switzerland; 2 PRBT-S, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Gene expression profiles of five consecutive stages of mouse B cell development were generated with high-density oligonucleotide arrays from as few as 2 × 104 ex vivo isolated and flow-cytometrically purified cells. Between 2.8% and 6.8% of all genes change on differentiation from one cellular stage to the next by at least twofold. The entire pathway involves differential expression of 10.7% of all genes. Previously known expression patterns of 15 genes (like surrogate light chain, RAG-1/2, MHC class II, mel-14 antigen) are confirmed. The gene expression patterns of the proliferating pre-BI and large pre-BII cells on the one hand, and the resting immature and mature B cells on the other hand, are most similar to each other. Small pre-BII cells display a pattern that is transitional between these two groups. Most of the genes expressed in early precursors are involved in general processes, like protein folding or cell cycle regulation, whereas more mature precursors express genes involved in more specific molecular programs (cell surface receptors, secreted factors, and adhesion molecules, among others). Between 19 and 139 genes share a given expression pattern. Combining knowledge about gene function and expression pattern allows identification of novel candidate genes potentially involved in self-maintenance of pre-BI cells, allelic exclusion and pre-B cell receptor signaling in large pre BII cells, cell-cycle arrest of small pre-BII cells, propensity toward apoptosis or anergization in immature B cells, propensity toward cell division and activation in mature B cells, and stage-specific interactions with stromal cells in the bone marrow.

[The sequence data described in this paper have been submitted to the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) under accession number GSE13. Online supplementary material available at www.genome.org.]

3 Present address: Max-von-Pettenhofer-Institut, Pettenhofer Str. 9A, 80336 Munich, Germany.

4 Corresponding authors.

12:98-111 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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