Early decisions in lymphoid development

Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York-Bronx, NY 10461, USA.
Current Opinion in Immunology (Impact Factor: 7.48). 05/2007; 19(2):123-8. DOI: 10.1016/j.coi.2007.02.007
Source: PubMed


Recent research suggests that lymphoid progenitors in the bone marrow comprise a heterogeneous cell population. This population first loses megakaryocyte/erythroid, and then granulocyte/macrophage, potential before committing to lymphoid lineages. B and T cells can originate by way of different pathways that appear to be used with varying frequencies in the animal. In the bone marrow, B cell specification and commitment is driven by the concerted action of transcription factors and IL-7 signaling. In the thymus, multipotent progenitors become committed to the T-cell lineage through the action of Notch1. The activated intracellular form of Notch1 suppresses transcription factors that can instruct myeloid cell fates, thereby directly coupling extracellular signaling with changes in transcriptional networks. In conclusion, although a lot is known about B and T cell commitment, more work needs to be done to clarify the earliest steps in lymphoid specification.

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Available from: Thomas Graf, Aug 31, 2015
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    • "During bone marrow B lymphopoiesis, B lymphocyte precursors undergo a strictly controlled process of differentiation, passing from pre–pro B to pro-B and then to pre-B stages, phenotypically characterized as fractions A–D (Hardy et al. 1991). Progressively, several molecules, including cKit, are downregulated while CD43 expression is also modulated on the surface of these cells (Hardy & Hayakawa 2001, Ye & Graf 2007). Subsequently, following the successful rearrangement of the B-cell receptor light chain genes, IgM is expressed on the surface of immature B-cells (Burrows et al. 2002). "
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    • "Macrophages possess both homeostatic and innate immune defense roles in metazoans, necessitating their continual production from hematopoietic precursors. The development of macrophages from progenitor cells, termed monopoiesis, occurs through the interplay between extracellular growth factors and intracellular transcription factors (Cantor and Orkin, 2002; Friedman, 2002; Ye and Graf, 2007; Zhu and Emerson, 2002). The key growth factors that regulate monopoiesis are colony-stimulating factor-1 (CSF-1) (Fixe and Praloran, 1997; Guilbert and Stanley, 1980; Stanley et al., 1997; Tushinski et al., 1982) and interleukin-34 (IL-34) (Chihara et al., 2010; Lin et al., 2008; Wei et al., 2010), which act through the CSF-1 receptor (CSF-1R) to regulate the survival, proliferation , and development of macrophages and their precursors (Hamilton, 1997; Pixley and Stanley, 2004). "
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