Developmental plasticity of lymphocytes

• Published in: Current opinion in immunology Vol. 20; no. 2; pp. 139 - 148
• Main Authors: Cobaleda, César, Busslinger, Meinrad
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2008
• Subjects: Allergy and Immunology; Cell Dedifferentiation; Cell Differentiation; Cell Lineage; Cytokines - physiology; Hematologic Neoplasms - genetics; Humans; Precursor Cells, B-Lymphoid - cytology; Precursor Cells, B-Lymphoid - immunology; Precursor Cells, B-Lymphoid - metabolism; Precursor Cells, T-Lymphoid - cytology; Precursor Cells, T-Lymphoid - immunology; Precursor Cells, T-Lymphoid - metabolism; Signal Transduction; Transcription Factors - metabolism
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2008.03.017

Experimental perturbation of signaling or transcription factor networks has been used to study the developmental potential of lymphoid progenitors, lineage-committed precursors and mature lymphocytes. Common lymphoid progenitors and uncommitted pro-T cells can be efficiently diverted into myeloid or erythroid lineages by ectopic cytokine signaling or retroviral expression of the myeloid C/EBPα or erythroid GATA1 transcription factor. Forced C/EBPα expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages. Notably, conditional inactivation of the B cell commitment factor Pax5 is sufficient to convert mature B cells into functional T cells via dedifferentiation to uncommitted progenitors. Together these experiments have uncovered an unanticipated developmental plasticity of lymphocytes, which may account for lineage switches observed in human malignancies.