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Blood, 1 January 2008, Vol. 111, No. 1, pp. 50-59.
Prepublished online as a Blood First Edition Paper on September 27, 2007; DOI 10.1182/blood-2007-07-099598.


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Submitted July 6, 2007
Accepted September 20, 2007

IL-15 regulates immature B cell homing in an Ly49D, IL-12, and IL-18 dependent manner

Gili Hart, Tamar Avin-Wittenberg, and Idit Shachar*

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

* Corresponding author; email: idit.shachar{at}weizmann.ac.il.

In order to complete their maturation and participate in the humoral immune response, immature B cells that leave the bone marrow are targeted to specific areas in the spleen, where they differentiate into mature cells. Previously, we showed that immature B cells actively down-regulate their integrin-mediated migration to lymph nodes or to sites of inflammation, enabling their targeting to the spleen for final maturation. This inhibition is mediated by IFN-{gamma}, which is transcribed and secreted at low levels by these immature B cells; IFN-{gamma} expression is extinguished following B cell maturation. Stimulation of the MHC class I receptor, Ly49D, triggers a signaling cascade that increases transcription of both IL-12 (p40) and IL-18; these, in turn, induce the secretion of IFN-{gamma}. In the present study, we demonstrate that Ly49D-dependent secretion of IL-12 and IL-18 induces IL-15 expression by immature B cells, and that these three factors together regulate IFN-{gamma} production that inhibits their ability to home to the lymph nodes or to sites of inflammation. Thus, IL-15 controls immature B cell homing, resulting in shaping the B cell repertoire to enable an efficient immune response.


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