Distinctive growth requirements and gene expression patterns distinguish progenitor B cells from pre-B cells.
Long-term bone marrow cultures have been useful in determining gene expression patterns in pre-B cells and in the identification of cytokines such as interleukin 7 (IL-7). We have developed a culture system to selectively grow populations of B lineage restricted progenitors (pro-B cells) from murine bone marrow. Pro-B cells do not grow in response to IL-7, Steel locus factor (SLF), or a combination of the two. c-kit, the SLF receptor, and the IL-7 receptor are both expressed by pro-B cells, indicating that the lack of response is not simply due to the absence of receptors. Furthermore, SLF is not necessary for the growth of pro-B cells since they could be expanded on a stromal line derived from Steel mice that produces no SLF. IL-7 responsiveness in pre-B cells is associated with an increase in n-myc expression and is correlated with immunoglobulin (Ig) gene rearrangements. Although members of the ets family of transcription factors and the Pim-1 kinase are expressed by pro-B cells, n-myc is not expressed. Pro-B cells maintain Ig genes in the germline configuration, which is correlated with a low level of recombination activating genes 1 and 2 (Rag-1 and 2) mRNA expression, but high expression of sterile mu and terminal deoxynucleotidyl transferase. Pro-B cells are unable to grow separated from the stromal layer by a porous membrane, indicating that stromal contact is required for growth. These results suggest that pro-B cells are dependent on alternative growth signals derived from bone marrow stroma and can be distinguished from pre-B cells by specific patterns of gene expression.
Faust
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Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
Saffran
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DC
Toksoz
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Williams
D A
DA
Witte
O N
ON
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology; D015851:Interleukin-7 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D011971:Receptors, Immunologic / Q000378:metabolism; D020395:Receptors, Interleukin-7
D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit