MRC National Institute for Medical Research, London
Science for Health
Migration into the right area of the spleen is crucial in B cell development
23 March 2010
B cells are a key part of the immune system, generating antibodies against pathogens. In mammals, the early phase of B cell development occurs in the bone marrow. Progenitor cells in the marrow differentiate through a series of steps into immature B cells, which then migrate out of the bone marrow, through the blood and into the spleen. Here these cells, now termed transitional B cells, complete their maturation into mature B cells.
Victor Tybulewicz (pictured) and co-workers in NIMR’s Division of Immune Cell Biology have investigated the mechanism behind this migration of immature B cells, and the functional consequences of such a migration. They discovered that a key step of the migration was the movement of cells from the red to the white pulp of the spleen, and that this movement was under the control of chemokines and the Rac GTPases. Furthermore, they went on to show that the migration into white pulp is critical for survival of immature/transitional B cells, and that this migration-dependent survival is a key feature in the process of positive selection of B cells.
Analysis of mice deficient in the Rac1 and Rac2 GTPases revealed an unexpected novel block in B cell development at the point of migration of immature B cells from the red to the white pulp of the spleen. Our work shows that this migration is tightly coupled to the process of B cell positive selection in which only B cells expressing a functional B cell antigen receptor in the form of cell surface bound immunoglobulin are able to exit the marrow, migrate to the white pulp of the spleen and complete their maturation into mature B cells
Victor Tybulewicz
B cells deficient in Rac2 GTPase
B cells (green) deficient in the Rac2 GTPase are largely unable to enter the white pulp of the spleen. The edges of the white pulp are identified by expression of the MadCAM-1 protein (red).
Original article
The research findings are published in full in:
Robert B. Henderson, Katarzyna Grys, Anne Vehlow, Carine de Bettignies, Agnieszka Zachacz, Tom Henley, Martin Turner, Facundo Batista, and Victor L. J. Tybulewicz. (2010)
A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival.
Journal of Experimental Medicine, epub ahead of print. Publisher abstract
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