期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：21
页码：8108-8113
DOI：10.1073/pnas.0402629101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：B lymphocytes can be activated by many different stimuli. However, the mechanisms responsible for the signaling and functional specificities of individual stimuli remain to be elucidated. Here, we have compared the contribution of the type 1 (p50-dependent) and type 2 (p52-dependent) NF-{kappa}B activation pathways to cell survival, proliferation, homotypic aggregation, and specific gene regulation of murine primary B lymphocytes. Whereas lipopolysaccharide (LPS) and B cell activation factor (BAFF) mainly activate the type 1 or type 2 pathways, respectively, CD40 ligand (CD40L) strongly activates both. Rescue of spontaneous apoptosis is diminished in p52-/- B cells after BAFF stimulation and in p50-/-c-Rel-/- B cells after LPS stimulation. Interestingly, significant CD40-induced B cell survival is still observed even in p50-/-c-Rel-/-p65-/+ B cells, which is correlated with the ability of CD40L to up-regulate Bcl-xL expression in these cells. CD40L- and LPS-induced B cell proliferation, as well as up-regulation of proliferation-related genes, however, are greatly reduced in c-Rel-/- and p50-/-c-Rel-/- B cells but are normal in p52-/- B cells. We have further demonstrated that both c-Rel and p52 are required for CD40-mediated B cell homotypic aggregation, which explains well why neither LPS nor BAFF has this function. Overall, our studies suggest that both type 1 and type 2 NF-{kappa}B pathways contribute to the gene expression and biological program unique for CD40 in B cell activation.
