Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture.
Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture.
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DOI：
10.1084/jem.187.2.147
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发表时间：
1998-01-19
期刊：
影响因子：
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通讯作者：
Siebenlist U
中科院分区：
文献类型：
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作者：
Franzoso G;Carlson L;Poljak L;Shores EW;Epstein S;Leonardi A;Grinberg A;Tran T;Scharton-Kersten T;Anver M;Love P;Brown K;Siebenlist U
p52是核因子（NF）-κB转录因子的一个亚单位，与p50关系最为密切。此前我们已经表明，当与Bcl - 3（IκB家族中一个特殊成员）结合时，p52而非p50同二聚体能够形成反式激活复合物。为了确定p52的非冗余生理作用，我们培育了p52缺陷型小鼠。缺失突变型小鼠针对T细胞依赖性抗原产生抗体的能力受损，这与次级淋巴器官中B细胞滤泡和滤泡树突状细胞网络的缺失以及无法形成生发中心是一致的。此外，脾脏边缘区被破坏。这些表型与在Bcl - 3基因敲除动物中观察到的表型在很大程度上重叠，但与p50基因敲除动物的表型不同，这支持了p52同二聚体和Bcl - 3形成具有生理相关性复合物的观点。过继转移实验进一步表明，这种复合物在抗原特异性免疫反应过程中的辅助细胞功能中可能至关重要。我们讨论了p52和Bcl - 3可能的作用，这些作用可能是这些蛋白质致癌潜能的基础，正如它们的基因在淋巴瘤中反复发生染色体易位所证明的那样。
p52 is a subunit of nuclear factor (NF)-κB transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the IκB family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.