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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2849-2857.
Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2004-03-0790.
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Submitted March 2, 2004
Accepted June 29, 2004
E47, IRF-4 and PU.1 synergize to induce B cell-specific activation of the Class II Transactivator promoter III (CIITA-PIII)
Nienke Van der Stoep*, Edwin Quinten, Marisa Marcondes Rezende, and Peter J Van den Elsen
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands
* Corresponding author; email: nvdstoep{at}lumc.nl.
In B cells, expression of CIITA and resulting MHCII is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells and monocytes. In this study we characterized the various regulatory elements and interacting factors of CIITA-PIII that account for specific activation in B-lymphocytes. We identified two E-box motifs and an EICE in CIITA-PIII to play a crucial role in the B cell-specific transcriptional regulation of CIITA. Abolishment of factor binding to these elements resulted in a strong reduction of CIITA-PIII activation in B cells only, whereas it did scarcely or not affect the activity of CIITA-PIII in activated T cells and monocytes. We show that in B cells E47 and PU.1/ IRF-4 interact with the E-box motifs and the EICE, respectively and act synergistically in the activation of CIITA-PIII. Moreover, functional inhibition of either E47 or IRF-4 resulted in strong reduction of CIITA-PIII activity in B-lymphocytes only. The finding that PU.1, IRF-4 and E47 play an important role in the B-cell mediated activation of CIITA-PIII provides a link between antigen presentation functions, and activation and differentiation events in B-lymphocytes.

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