Load and lock: the molecular mechanisms of B-lymphocyte commitment.
The maturation of B-lymphoid cells from hematopoietic stem cells in the bone marrow is a complex process under control of interplay between extrinsic and intrinsic factors. In addition to serving as a model for normal cell differentiation, disturbances in this process results in immunodeficiencies and malignancies, such as leukemia and lymphoma, making the subject of high relevance for modern medicine. Although the process of B lymphopoiesis has been under intense investigation, recent methodological developments within the area of cell sorting, genome-wide expression, and DNA-binding analysis has allowed for a rapid development of the understanding of B-lymphocyte differentiation. This has suggested that the path to B-lymphoid cell fate may be initiated by lineage priming reflected in the expression of lymphoid associated genes already in multipotent hematopoietic progenitors. Upon differentiation, the gene expression profile is changed to involve an increasing number of B-lineage-restricted genes linked to loss of alternative developmental potentials and B-lineage commitment. This review focuses on the molecular regulation of early B-lymphoid development and aims to provide an up to date summary of the current status of the research area.
Zandi
Sasan
S
Experimental Hematopoiesis Unit, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Bryder
David
D
Sigvardsson
Mikael
M
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D002471:Cell Transformation, Neoplastic; D005786:Gene Expression Regulation / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D015398:Signal Transduction / Q000276:immunology
D000943:Antigens, Differentiation