Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses.
Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses.
复制标题
DOI：
10.1084/jem.187.2.185
复制
发表时间：
1998-01-19
影响因子：
15.3
通讯作者：
Bravo, R
中科院分区：
文献类型：
--
作者：
Caamano, J H;Rizzo, C A;Durham, S K;Barton, D S;Raventos-Suarez, C;Snapper, C M;Bravo, R
nfkb 2基因是转录因子Rel/NF-κB家族的成员。该基因的COOH末端缺失和重排与人类皮肤T细胞淋巴瘤、慢性淋巴细胞白血病和多发性骨髓瘤的发生有关。为了进一步研究NF-κB2的功能，我们通过同源重组产生了携带nfkb 2基因种系突变的突变小鼠。NF-κB2缺陷小鼠的脾脏、骨髓和淋巴结中的B细胞区室显著减少。此外，突变小鼠的脾脏和淋巴结呈现出改变的结构，其特征在于弥漫性的、不规则的B细胞区域和不连续的滤泡周围边缘区和外套层区;脾脏中次级生发中心的形成也受损。NF-κB2缺陷型B细胞的增殖在对脂多糖、抗IgD-葡聚糖和CD 40的反应中中度降低，但成熟和免疫球蛋白转换正常。然而，nfkb 2（−/−）动物对T细胞依赖性和非依赖性抗原的免疫应答不足。这些发现表明NF-κB2在维持外周B细胞群、体液应答和正常脾结构中具有重要作用。
The nfkb2 gene is a member of the Rel/NF-κB family of transcription factors. COOH-terminal deletions and rearrangements of this gene have been associated with the development of human cutaneous T cell lymphomas, chronic lymphocytic leukemias, and multiple myelomas. To further investigate the function of NF-κB2, we have generated mutant mice carrying a germline mutation of the nfkb2 gene by homologous recombination. NF-κB2–deficient mice showed a marked reduction in the B cell compartment in spleen, bone marrow, and lymph nodes. Moreover, spleen and lymph nodes of mutant mice presented an altered architecture, characterized by diffuse, irregular B cell areas and the absence of discrete perifollicular marginal and mantle zones; the formation of secondary germinal centers in spleen was also impaired. Proliferation of NF-κB2–deficient B cells was moderately reduced in response to lipopolysaccharide, anti-IgD-dextran, and CD40, but maturation and immunoglobulin switching were normal. However, nfkb2 (−/−) animals presented a deficient immunological response to T cell–dependent and –independent antigens. These findings indicate an important role of NF-κB2 in the maintenance of the peripheral B cell population, humoral responses, and normal spleen architecture.