Itpkb, Crucial Gene In Immune System Development? Publication Of ULB-IRIBHM In PNAS

Main Category: Immune System / Vaccines
Also Included In: Genetics
Article Date: 11 Sep 2007 - 0:00 PDT

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The researchers, including Yoann Marechal, a medical doctor of the ULB, have identified several abnormalities in the development and the function of B lymphocytes in Itpkb-deficient mice. The results of this research have been published in the Proceedings of the National Academy of Sciences USA (PNAS).

The researchers of the IRIBHM have prooved, by the use of these genetically modified mice, that those abnormalities of B lymphocytes development and function are the result of an overexpression of molecule furthering apoptosis. The consequence of this overexpression is thus a decreased survival of the B lymphocytes and defect in antibody production in response to certain agents.

The IRIBHM's team has also suggested a mechanism by which Inositol 1,3,4,5 tetrakisphosphate, the product generated by Itpkb, plays a significant role in the development and function of B lymphocytes : it controls the subcellular localization of the Rasa 3 enzyme, one of its intracellular receptors. Indeed, production of inositol 1,3,4,5-tetrakisphosphate in the cell results in the dissociation of the Rasa 3 receptor from the cell membrane and its inactivation.

This work follows other research still under way at the IRIBHM and focused on the unexpected but significant role of the Itpkb enzyme in T lymphocytes development. Considering the localization of the Itpkb gene in a region of the chromosom 1 known in man and mouse to contain several predisposition genes to autoimmune disease and considering this gene's function in T and B lymphocytes development, the researchers of the IRIBHM investigate the hypothesis according to which alterations in this Itpkb gene could eventuallly favour the appearance of autoimmune disease (Disseminated Lupus Erythmatosus, type 1 diabetes,…).

This research, recently published in PNAS, has been done in collaboration with teams from the ULB (IRIBHM, IBMM), the Universite de Geneve, Harvard University and Bristol University.

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