Caamaño J H, Rizzo C A, Durham S K, Barton D S, Raventós-Suárez C, Snapper C M, Bravo R
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
J Exp Med. 1998 Jan 19;187(2):185-96. doi: 10.1084/jem.187.2.185.
The nfkb2 gene is a member of the Rel/NF-kappa B 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-kappa B2, we have generated mutant mice carrying a germline mutation of the nfkb2 gene by homologous recombination. NF-kappa B2-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-kappa B2-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-kappa B2 in the maintenance of the peripheral B cell population, humoral responses, and normal spleen architecture.
nfkb2基因是转录因子Rel/NF-κB家族的成员。该基因的羧基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nfkb2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细胞区室明显减少。此外，突变小鼠的脾脏和淋巴结呈现出结构改变，其特征为弥漫性、不规则的B细胞区域以及离散的滤泡周围边缘区和套区缺失；脾脏中次级生发中心的形成也受到损害。NF-κB2缺陷的B细胞对脂多糖、抗IgD-葡聚糖和CD40的增殖反应适度降低，但成熟和免疫球蛋白类别转换正常。然而，nfkb2(-/-)动物对T细胞依赖性和非依赖性抗原的免疫反应存在缺陷。这些发现表明NF-κB2在维持外周B细胞群体、体液反应和正常脾脏结构中起重要作用。
