Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells
Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells
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DOI：
10.1111/cei.12604
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发表时间：
2015-06-01
影响因子：
4.6
通讯作者：
Dullaers, M.
中科院分区：
文献类型：
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作者：
De Bruyne, R.;Bogaert, D.;Dullaers, M.
钙调神经磷酸酶抑制剂（CNI），经常用于实体器官移植患者，已知抑制T细胞增殖，但其对体液免疫的影响研究少得多。在免疫球蛋白（IG）A-或IgG/IgE-促进条件下培养来自健康成人供体的总和幼稚B细胞，并增加环孢菌素、他克莫司、雷帕霉素或甲基强的松龙的剂量。测试了对细胞数量、细胞分裂、浆母细胞分化和类别转换的影响。为了检测对T滤泡辅助细胞（Tfh）分化的影响，将初始CD 4（+）T细胞与白细胞介素（IL）-12和滴定的免疫抑制药物（IS）浓度一起培养。总B细胞功能不受CNI的影响。然而，幼稚B细胞增殖抑制环孢素和CNI降低浆母细胞分化。两个CNI抑制伊加，而只有环孢素抑制IgE类转换。雷帕霉素对B细胞功能有较强的抑制作用。引人注目的是，甲基强的松龙，增加浆母细胞分化和IgE类转换从幼稚B细胞。Tfh细胞的分化随着IS剂量的增加而降低。CNI通过抑制幼稚B细胞直接影响体液免疫。CNI，以及雷帕霉素和甲基强的松龙，抑制Tfh从幼稚CD 4（+）T细胞的体外分化。鉴于其对B细胞功能和Tfh细胞分化的有效抑制作用，雷帕霉素可能是实体器官移植后B细胞介导的并发症的管理中的感兴趣的候选者。
Calcineurin inhibitors (CNI), used frequently in solid organ transplant patients, are known to inhibit T cell proliferation, but their effect on humoral immunity is far less studied. Total and naive B cells from healthy adult donors were cultured in immunoglobulin (Ig)A- or IgG/IgE-promoting conditions with increasing doses of cyclosporin, tacrolimus, rapamycin or methylprednisolone. The effect on cell number, cell division, plasmablast differentiation and class-switching was tested. To examine the effect on T follicular helper (Tfh) cell differentiation, naive CD4(+) T cells were cultured with interleukin (IL)-12 and titrated immunosuppressive drug (IS) concentrations. Total B cell function was not affected by CNI. However, naive B cell proliferation was inhibited by cyclosporin and both CNI decreased plasmablast differentiation. Both CNI suppressed IgA, whereas only cyclosporin inhibited IgE class-switching. Rapamycin had a strong inhibitory effect on B cell function. Strikingly, methylprednisolone, increased plasmablast differentiation and IgE class-switching from naive B cells. Differentiation of Tfh cells decreased with increasing IS doses. CNI affected humoral immunity directly by suppressing naive B cells. CNI, as well as rapamycin and methylprednisolone, inhibited the in-vitro differentiation of Tfh from naive CD4(+) T cells. In view of its potent suppressive effect on B cell function and Tfh cell differentiation, rapamycin might be an interesting candidate in the management of B cell mediated complications post solid organ transplantation.