| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,#
* Department of Immunology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway;
Department of Informatics, University of Bergen, Bergen, Norway;
Institute of Pathology, Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway;
Institute of Pathology, University of Wurzburg, Wurzburg, Germany;
¶ Metabolism Branch, National Cancer Institute, Bethesda, MD 20892; and
|| Centre for Biomedicine, University of Oslo, Oslo, Norway; and
# Computational Biology Unit, University of Bergen, Bergen, Norway
We have characterized several stages of normal human B cell development in adult bone marrow by gene expression profiling of hemopoietic stem cells, early B (E-B), pro-B, pre-B, and immature B cells, using RNA amplification and Lymphochip cDNA microarrays (n = 6). Hierarchical clustering of 758 differentially expressed genes clearly separated the five populations. We used gene sets to investigate the functional assignment of the differentially expressed genes. Genes involved in VDJ recombination as well as B lineage-associated transcription factors (TCF3 (E2A), EBF, BCL11A, and PAX5) were turned on in E-B cells, before acquisition of CD19. Several transcription factors with unknown roles in B lymphoid cells demonstrated interesting expression patterns, including ZCCHC7 and ZHX2. Compared with hemopoietic stem cells and pro-B cells, E-B cells had increased expression of 18 genes, and these included IGJ, IL1RAP, BCL2, and CD62L. In addition, E-B cells expressed T/NK lineage and myeloid-associated genes including CD2, NOTCH1, CD99, PECAM1, TNFSF13B, and MPO. Expression of key genes was confirmed at the protein level by FACS analysis. Several of these Ags were heterogeneously expressed, providing a basis for further subdivision of E-B cells. Altogether, these results provide new information regarding expression of genes in early stages of human B cell development.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Norwegian Cancer Society, the Norwegian Research Council, and the Functional Genomics (FUGE) Program of the Norwegian Research Council.
2 Address correspondence and reprint requests to Dr. Erlend B. Smeland, Department of Immunology, Institute of Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, 0310 Oslo, Norway. E-mail address: erlend.bremertun.smeland{at}rr-research.no
3 Abbreviations used in this paper: BM, bone marrow; HSC, hemopoietic stem cell; E-B, early B; IM-B, immature B; CLP, common lymphoid progenitors; MPO, myeloperoxidase; FDR, false discovery rate; GO, Gene Ontology; GC, germinal center; MEF, myocyte enhancer factor; MLP, multilineage progenitor cells; ALL, acute lymphoblastic leukemia.
4 The online version of this article contains supplemental material.
This article has been cited by other articles:
|
|
 |
|
  T. Kuwata and T. Nakamura BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body Genes Cells, September 1, 2008; 13(9): 931 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Johnson, N. Shah, A. A. Bajer, and T. W. LeBien IL-7 Activates the Phosphatidylinositol 3-Kinase/AKT Pathway in Normal Human Thymocytes but Not Normal Human B Cell Precursors J. Immunol., June 15, 2008; 180(12): 8109 - 8117. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
