Dendritic cells directly modulate B cell growth and differentiation
Dendritic cells directly modulate B cell growth and differentiation
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DOI：
10.1002/jlb.66.2.224
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发表时间：
1999-08-01
影响因子：
5.5
通讯作者：
Brière, F
中科院分区：
文献类型：
--
作者：
Dubois, B;Bridon, JM;Brière, F
位于粘膜上皮内的朗格汉斯细胞或树突状细胞（DC）的主要特征是在组织损伤后捕获外源抗原并随后启动免疫应答。当通过引流输入淋巴迁移到近端次级淋巴器官时，DC处理抗原。在次级淋巴器官的副皮质区域内，DC [在本定位中称为交错树突状细胞（IDC）]选择罕见的抗原特异性T和B细胞[1，2]。IDC具有刺激抗原特异性初始T细胞增殖、分泌细胞因子和表达CD 40 L的独特能力[3-5]。在鼠模型中，免疫组织学研究表明，原发性T细胞依赖性B细胞应答在T细胞/IDC富集区域内启动[6]。活化的T细胞刺激抗原特异性幼稚B细胞增殖并分化为生发中心创始细胞或短寿命浆细胞，主要产生免疫球蛋白M（IgM）[7]。生发中心反应开始于生发中心创始细胞在初级卵泡的定植。已经鉴定出抗原转运细胞，其捕获淋巴中的免疫复合物并将这些复合物移动到滤泡内的滤泡树突状细胞网络上[8]。这种抗原转运细胞的性质尚未正式确定。在滤泡内，滤泡树突状细胞（可能不是造血来源）保留免疫复合物，从而允许B细胞内吞、加工并将抗原呈递给CD 4 T细胞。在暗区中心母细胞的强烈增殖之后，在生发中心反应期间发生不可逆事件，其导致对抗原具有高亲和力的同种型转换的B细胞，其最终分化成记忆B细胞或浆细胞。除了DC在启动细胞免疫应答中的关键作用外[4]，一些实验强烈支持它们直接参与体液应答的调节。我们的研究现在提供了证据表明，人DC在体外直接与B细胞相互作用，并在其分化的各个阶段调节成熟B细胞应答。
A cardinal feature of Langerhans cells or dendritic cells (DC) located within the mucosal epithelium is to capture foreign antigens after tissue injury and subsequently initiate immune responses. While migrating through the draining afferent lymph into the proximal secondary lymphoid organ, DC process the antigens. Within paracortical areas of the secondary lymphoid organs, DC [referred to in this localization as interdigitating dendritic cells (IDC)] select the rare antigen-specific T and B cells [1, 2]. IDC have the unique capacity to stimulate antigen-specific naive T cells to proliferate, secrete cytokines, and express CD40L [3–5]. In murine models, immunohistological studies have demonstrated that primary T cell-dependent B cell responses were initiated within the T cell/IDC-rich areas [6]. Activated T cells stimulate antigen-specific naive B cells to proliferate and to differentiate into germinal center founder cells or into short-lived plasma cells producing essentially immunoglobulin M (IgM)[7]. The germinal center reaction starts with the colonization of primary follicles by germinal center founder cells. Antigen transporting cells have been identified that trap immune complexes in the lymph and move these complexes onto the follicular dendritic cell network within the follicles [8]. The nature of such antigen transporting cells has not yet been formally identified. Within the follicles, follicular dendritic cells, which are probably not of hemopoietic origin, retain immune complexes, thus allowing B cells to endocytose, process, and present the antigen to CD4 T cells. After intense proliferation of centroblasts in the dark zone, irreversible events occur during the germinal center reaction that lead to isotype-switched B cells with high affinity for the antigen that eventually differentiate into either memory B cells or plasma cells. Apart from the critical role of DC in the initiation of cellular immune responses [4], several experiments strongly support their direct involvement in the regulation of humoral responses. Our studies now provide evidence that human DC directly interact with B cells in vitro and regulate mature B cell responses at various stages of their differentiation.