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Synergism between NF-B1/p50 and Notch2 during the Development of Marginal Zone B Lymphocytes¹

Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129

NF-B1 and Notch2 are both required for the development of marginal zone (MZ) B cells. Analysis of B lymphocyte development in mice that are doubly heterozygous at the Notch2 and NF-B1 loci revealed synergism between Notch2 and NF-B1 during MZ B cell development. Two known transcriptional targets of the Notch pathway, Hes-5 and Deltex-1, were found to be preferentially expressed in MZ B cells and regulated by NF-B1. These studies provide in vivo evidence for a genetic interaction between the Notch and NF-B pathways.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI 064930 and CA102793.

² S.T.M. and A.C. were equal contributors.

³ Address correspondence and reprint requests to Dr. Shiv Pillai, Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129. E-mail address: pillai{at}helix.mgh.harvard.edu

⁴ Abbreviations used in this paper: IKK, IB kinase; FO, follicular; MZ, marginal zone; Btk, Bruton’s tyrosine kinase; BAFF, B cell-activating factor of the TNF family; BAFF-R, BAFF receptor; FO-I, FO type I; FO-II, FO type II; MZP, MZ precursor; NF, newly formed.

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