Differentiation of B cells in the bovine. Role of cytokines in immunoglobulin isotype expression
Differentiation of B cells in the bovine. Role of cytokines in immunoglobulin isotype expression
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DOI：
10.1016/s0165-2427(96)05684-x
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发表时间：
1996-11-01
影响因子：
1.8
通讯作者：
Estes, DM
中科院分区：
文献类型：
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作者：
Estes, DM
已知的细胞因子如干扰素-γ、白介素4和转化生长因子-β通过正向或负向调节小鼠和人类生殖系C-H转录来调节免疫球蛋白类的转换。在这里，我们展示了在蛋白质水平上，利用B细胞激活和细胞因子组合的不同模式，在牛身上也有类似的调节机制。利用抗原-受体交联法或有丝分裂原(商陆有丝分裂原)共刺激，我们证明了重组牛IL-4在体外上调了IgM、Ig G(1)和Ig E的表达。RboIL-4对Ig G(1)和Ig E产生的上调作用可被rboIL-4以剂量依赖的方式抑制。使用类似的方法，我们还研究了在存在或不存在包括IL-10和IL-2在内的各种辅助因子的情况下，TGB-β对IgA产生的影响。我们发现，在与有丝分裂原或福尔马林固定的Cowan菌株I(SAC)共同培养时，转化生长因子-β不会单独上调未承诺前体(SIGM(+))的IgA产生，但在IL-2和IL-10同时存在的情况下，确实对IgA的产生有积极影响。这些观察表明，在存在细胞因子的情况下，使用经典B细胞激活剂的不同T非依赖性共刺激模式不会导致牛B细胞产生不同的Ig G亚型或Ig E。综上所述，这些结果表明，单个细胞因子调节牛的同型表达。
Cytokines such as IFN-gamma, IL-4 and TGF-beta, are known to regulate Ig class switching by positively or negatively regulating germline C-H transcription in the mouse and human. Here we show at the protein level that similar regulatory mechanisms are in place in the bovine using various modes of B cell activation and cytokine combinations. Using antigen-receptor cross-linkage or mitogen (pokeweed mitogen) costimulation, we demonstrate that recombinant bovine IL-4 upregulates the expression of IgM, IgG(1) and IgE in vitro. Upregulation of IgG(1) and IgE production by rboIL-4 is inhibited in a dose-dependent manner by the addition or rboIFN-gamma to the cultures. Using similar methodologies, we have also investigated the effects of TGB-beta on IgA production in the presence or absence of various cofactors including IL-10 and IL-2. We find that TGF-beta will not solely upregulate IgA production from noncommitted precursors (sIgM(+)) in coculture with mitogen or with formalin fixed Staphylococcus cowan Strain I(SAC), but does have positive effects on IgA production in the presence of both IL-2 and IL-10. These observations suggest that different modes of T-independent costimulation using classical B cell activators does not result in differential IgG subisotype or IgE production by bovine B cells in the presence of cytokines. Together these results suggest that individual cytokines regulate isotype expression in cattle.