Banchereau J, Bazan F, Blanchard D, Brière F, Galizzi J P, van Kooten C, Liu Y J, Rousset F, Saeland S
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Annu Rev Immunol. 1994;12:881-922. doi: 10.1146/annurev.iy.12.040194.004313.
CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
CD40是一种整合膜蛋白，存在于B淋巴细胞、树突状细胞、滤泡树突状细胞、造血祖细胞、上皮细胞和癌细胞表面。它是一种由277个氨基酸组成的45 - 50 kDa糖蛋白，属于肿瘤坏死因子受体超家族成员。CD40基因定位于人类染色体20q11 - 2 - q13 - 2。CD40与一种配体（CD40 - L）结合，CD40 - L是一种由261个氨基酸组成的约35 kDa糖蛋白，属于肿瘤坏死因子超家族成员。CD40 - L基因定位于人类染色体Xq24。这种CD40 - L在活化的T细胞上表达，主要是CD4 + T细胞，但也有一些CD8 + T细胞以及嗜碱性粒细胞/肥大细胞。CD40 - L在X连锁高IgM综合征中存在缺陷。用固定化抗CD40或表达CD40 - L的细胞使CD40交联可诱导B细胞强烈增殖，添加IL - 4或IL - 13可促使产生因子依赖性的长期正常人B细胞系，并在同种型转换后分泌IgE。添加IL - 10会导致免疫球蛋白大量产生，但细胞增殖有限。IL - 10诱导幼稚B细胞产生IgG3、IgG1和IgA1，进一步添加转化生长因子β可促使分泌IgA2。有几条证据表明，B细胞的CD40依赖性激活对于生发中心内记忆B细胞的产生很重要：（i）在IL - 4存在下培养的CD40激活的生发中心B细胞获得记忆B细胞表型，（ii）CD40激活的B细胞可进行同种型转换，（iii）CD40 - L缺陷导致高IgM综合征，其特征为次级淋巴器官滤泡中缺乏生发中心以及缺乏IgG、IgA和IgE，（iv）次级滤泡中存在CD40 - L阳性T细胞。胸腺上皮细胞、活化的单核细胞和树突状细胞表达CD40抗原，这可能参与这些细胞增强细胞因子的产生，从而促进T细胞增殖。最后，由于肿瘤坏死因子受体家族的其他成员已被证明可结合多种配体，所以CD40有可能结合其他配体，这些配体可能在不同细胞类型（如造血细胞或上皮细胞）上触发CD40。
