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We have identified a key gene in ensuring that our immune defences develop infection-fighting cells. No cells of the adaptive immune system develop in the absence of the gene Bcl11a. Cells of the adaptive immune system, B cells, T cells and NK cells, all share a common ancestor, or lymphoid progenitor.
Bcl11a is important for development of some immune cells in mouse embryos and we looked at the role of this gene in adult mice by knocking out Bcl11a and looking at development of the immune system cells. To our surprise no cells of the adaptive system developed. It is perhaps the first time that anyone has found a single gene that is absolutely essential for development of cells of our entire adaptive immune system.
The protein produced by Bcl11a is part of a network of components that regulate cell development and the imbalance caused by a lack of Bcl11a leads to the death of the progenitor cells of the adaptive immune system. By contrast, overactivity of Bcl11a is known to cause lymphomas. One member of the Bcl11a network is p53, known to be important in controlling cell division and, when mutated, important in driving cancer development. If p53 also is inactivated in mice that lack Bcl11a, some cells of the immune system develop. Uncovering these interactions will drive a better understanding of disease of the immune system.
Bcl11a also has a role in development of oxygen-carrying red blood cells: in 2011, researchers showed that silencing Bcl11a in mice could reverse sickle-cell disease.
NK ; B cells ; T cells ; animal models ; lymphocytes, ; adaptive immunity ; knockouts ; lymphoma
Li P, Burke S, Wang J, Chen X, Ortiz M, Lee SC, Lu D, Campos L, Goulding D, Ng BL, Dougan G, Huntly B, Gottgens B, Jenkins NA, Copeland NG, Colucci F and Liu P Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science (New York, N.Y.) 2010; 329; 5987; 85-9
Liu P, Li P, Burke S. Critical roles of Bcl11b in T-cell development and maintenance of T-cell identity. Immunol Rev. 2010 Nov;238(1):138-49.