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干貨分享 | 淋巴細胞和NK細胞，是如何生成的？
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淋巴細胞和NK細胞的生成 Lymphocyte and NK Cell Production CLP被認為能產(chǎn)生B淋巴細胞、T淋巴細胞和NK細胞。骨髓中B淋巴細胞和T淋巴細胞祖細胞的發(fā)育與抗原無關。SCF和Flt3L似乎都參與了小鼠早期淋巴系祖細胞的生成。 The CLP is believed to give rise to B lymphocytes, T lymphocytes, and NK cells.16 The development of B lymphocyte and T lymphocyte progenitors in bone marrow is antigenindependent. Both SCF and Flt3L appear to be involved in the production of early lymphoid progenitor cells in mice. B淋巴細胞祖細胞在大多數(shù)哺乳動物的骨髓中，在犬、豬和反芻動物的佩耶氏結(jié)中，以及在鳥類的法氏囊中生成成熟的、未成熟的B淋巴細胞。 大約2到3天，前B淋巴細胞在骨髓中發(fā)育為成熟的幼稚B淋巴細胞并進入循環(huán)。在骨髓中生成的B淋巴細胞中，只有不到20%成為外周成熟B淋巴細胞池的一部分，大多數(shù)細胞在骨髓或進入血液后被淘汰，B淋巴細胞也可以在成年動物外周血的淋巴組織中增殖。 與其他血細胞一樣，骨髓和淋巴器官的微環(huán)境對淋巴細胞的生成很重要�？乖舾械谋砻婷庖咔虻鞍钻栃訠淋巴細胞的生成以免疫球蛋白基因位點的連續(xù)重排和表面蛋白的選擇性表達為標志。 盡管許多細胞因子（包括SCF、Flt3L、SDF-1和IGF）參與骨髓中B淋巴細胞的生成，但IL-7似乎是一個特別重要的正生長因子。B淋巴細胞的生成受到多種因素的抑制，包括TGF-β、IFN-α、IFN-β和IFN-γ。 B lymphocyte progenitors produce mature, naive B lymphocytes in the marrow in most mammals, in specialized ileal Peyer’s patches in dogs, pigs, and ruminants, and in the bursa of Fabricius in birds. Approximately 2 to 3 days arerequired for pre-B lymphocytes to develop into mature, naive B lymphocytes in the marrow and enter the circulation. Less than 20% of B lymphocytes produced in the marrow become part of the peripheral mature B lymphocyte pool, with most of the cells being culled in the bone marrow or after their entry into blood. B lymphocytes also proliferate in peripheral lymphoid tissues in adults. As with other blood cells, the microenvironment of the marrow and lymphoid organs is important for lymphopoiesis. The production of antigen-sensitive, surface-immunoglobulin-positive B lymphocytes is marked by successive rearrangements of the immunoglobulin gene loci and selective expression of surface proteins. Although a number of cytokines—including SCF, Flt3L, SDF-1, and IGF—are involved in B lymphocyte production in marrow, IL-7 appears to be an especially important positive growth factor. B lymphocyte lymphopoiesis is inhibited by several factors, including TGF-β, IFN-α, IFN-β, and IFN-γ. 哺乳動物次級淋巴器官T淋巴細胞區(qū)的抗原刺激可以激活循環(huán)B淋巴細胞，然后遷移到淋巴結(jié)、佩耶氏結(jié)和脾臟的濾泡。B淋巴細胞的活化和分化為漿母細胞，是由微生物產(chǎn)物、細胞因子和結(jié)合在T淋巴細胞和樹突狀細胞表面分子組合誘導的。漿母細胞可以在生成它們的淋巴器官中發(fā)育為漿細胞，也可以通過血液遷移并在周圍組織或骨髓中發(fā)育為漿細胞。SDF-1將循環(huán)漿母細胞吸引到骨髓，包括SDF-1和IL-6在內(nèi)的因子通過阻止細胞凋亡來促進漿細胞的發(fā)育。 Recirculating B lymphocytes are activated by antigenic stimulation in the T lymphocyte region of secondary lymphoid organs, followed by migration to the cortex in lymph nodes and to follicles in jejunal Peyer’s patches and the spleen in mammals. B lymphocyte activation and differentiation into plasmablasts is induced by combinations of microbial products, cytokines, and molecules bound to the surfaces of T lymphocytes and dendritic cells. Plasmablasts can develop into plasma cells in the lymphoid organs where they are produced or can migrate through blood and develop into plasma cells in peripheral tissues or bone marrow. SDF-1 attracts circulating plasmablasts to the bone marrow, and factors including SDF-1 and IL-6 promote plasma cell development by preventing apoptosis. T淋巴細胞祖細胞離開骨髓，遷移到胸腺。這些細胞的歸處取決于它們與胸腺內(nèi)皮細胞上各種粘附分子的相互作用以及胸腺基質(zhì)細胞生成的特異性趨化因子。 T淋巴細胞祖細胞在胸腺微環(huán)境和胸腺產(chǎn)生的生長因子(包括Flt3L和IL-7)的影響下發(fā)育成T淋巴細胞。哺乳動物胸腺成熟后，T淋巴細胞會聚集在淋巴結(jié)皮質(zhì)旁區(qū)、脾臟小動脈周圍淋巴結(jié)和佩耶氏結(jié)濾泡間區(qū)。 T lymphocyte progenitors leave the marrow and migrate to the thymus. Homing of these cells to the thymus depends on their interaction with various adhesion molecules on thymic endothelial cells and the production of specific chemotactic factors by thymic stromal cells. T lymphocyte progenitors develop into T lymphocytes under the influence of the thymic microenvironment and growth factors (including Flt3L and IL-7) produced in the thymus. After maturation in the thymus, T lymphocytes accumulate within paracortical areas of lymph nodes, periarteriolar lymphoid sheaths of the spleen, and the interfollicular areas of jejunal Peyer’s patches in mammals. 大多數(shù)NK細胞是由骨髓中的祖細胞生成的，它們在骨髓中經(jīng)過一周或更久時間的擴增和成熟，然后釋放到血液中。控制其產(chǎn)生的生長因子需要進一步的表征，但SCF、IL-2、IL-7和IL-15可以在體外刺激NK細胞從祖細胞發(fā)育而來。NK細胞亞群也在胸腺和其他可能的器官，如淋巴結(jié)、肝臟和脾臟中發(fā)育。這些部位可能依賴于骨髓來源的祖細胞和/或未成熟的NK細胞從血液中進入這些器官，它們在微環(huán)境的影響下成熟。 Most NK cells are produced from progenitor cells in the bone marrow, where they undergo expansion and maturation for a week or more before their release into the blood.Growth factors controlling their production need further characterization, but SCF, IL-2, IL-7, and IL-15 can stimulate NK cell development from progenitor cells in vitro.Subsets of NK cells also develop in the thymus and possibly other organs, such as lymph nodes, liver, and spleen. These sites may depend on the trafficking of bone marrow–derived progenitor cells and/or immature NK cells into these organs from the blood, where they mature under the influence of microenvironmental factors. |
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