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Medical Immunology

, 3:1

First Online: 29 March 2004Received: 12 December 2003Accepted: 29 March 2004DOI: 10.1186-1476-9433-3-1

Cite this article as: Feng, B., Cheng, S., Pear, W.S. et al. Med Immunol 2004 3: 1. doi:10.1186-1476-9433-3-1

Abstract

Members of the NF-kB transcription factor family are differentially expressed in the B cell lineage. Disruption of individual or two NF-kB subunits exhibits distinct defects in B lymphocyte development, activation, and survival. However, the role each NF-kB plays during B cell development has been obscured by molecular compensation. To address this issue, a trans-dominant form of IkBα was transduced into bone marrow cells to act as a pan-inhibitor of NF-kB using a retroviral system. While the development of T-lymphocytes and myeloid cell lineages was not grossly affected by the transduced IkBα gene, a significant reduction in the number and percentage of B lineage cells was apparent in IkBα transduced chimeric mice. IkBα expression decreased the percentage of pre-B and immature B cell subsets in the bone marrow and further impaired the development of follicular mature B cells and marginal zone B cells in the periphery. Introduction of the Bcl-X transgene completely restored the pre-B and immature B cell pool in the bone marrow. However, despite a significant improvement of overall viability of the B cell lineage, Bcl-X expression was insufficient to overcome the maturation block resulting from NF-kB inhibition. Together, our study suggests that NF-kB activity is required for two distinct checkpoints during B cell development: one is for pre-B-immature B cell viability, the other is to provide both survival and maturation signals to ensure the proper development of follicular mature B cells.

KeywordsNF-kB IkBα Bcl-X B cell development retroviral gene transduction Electronic supplementary materialThe online version of this article doi:10.1186-1476-9433-3-1 contains supplementary material, which is available to authorized users.





Autor: Biao Feng - Shuhua Cheng - Warren S Pear - Hsiou-Chi Liou

Fuente: https://link.springer.com/







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