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Cell-Autonomous Role for NF-B in Immature Bone Marrow B Cells¹

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

The NF-B transcription factors have many essential functions in B cells, such as during differentiation and proliferation of Ag-challenged mature B cells, but also during final maturation of developing B cells in the spleen. Among the various specific functions NF-B factors carry out in these biologic contexts, their ability to assure the survival of mature and maturing B cells in the periphery stands out. Less clear is what if any roles NF-B factors play during earlier stages of B cell development in the bone marrow. Using mice deficient in both NF-B1 and NF-B2, which are thus partially compromised in both the classical and alternative activation pathways, we demonstrate a B cell-autonomous contribution of NF-B to the survival of immature B cells in the bone marrow. NF-B1 and NF-B2 also play a role during the earlier transition from proB to late preB cells; however, in this context these factors do not act in a B cell-autonomous fashion. Although NF-B1 and NF-B2 are not absolutely required for survival and progression of immature B cells in the bone marrow, they nevertheless make a significant contribution that marks the beginning of the profound cell-autonomous control these factors exert during all subsequent stages of B cell development. Therefore, the lifelong dependency of B cells on NF-B-mediated survival functions is set in motion at the time of first expression of a full BCR.

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 funds from the intramural program of the National Institute of Allergy and Infectious Diseases.

² Address correspondence and reprint requests to Dr. Ulrich Siebenlist, National Institutes of Health, Building 10, Room 11B15A, Bethesda, MD 20892-1876. E-mail address: USiebenlist{at}niaid.nih.gov

³ Abbreviations used in this paper: BAFF, B cell-activating factor of the TNF family; dKO, double knockout; TACI, transmembrane activator and calcium modulator and cyclophilin ligand interactor; IKK, inhibitor of B kinase; WT, wild type; HSA, heat-stable Ag; BCMA, B cell maturation Ag.