McIntyre T M, Kehry M R, Snapper C M
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814.
J Immunol. 1995 Apr 1;154(7):3156-61.
The parameters necessary for induction of high-rate IgA class switching are unknown. Thus, although TGF-beta is switch factor for the IgA class, the percentage of membrane (m)IgA+ cells generated in vitro in response to TGF-beta and various individual modes of B cell activation is limited to 1 to 2% of the total B cell population, a percentage far below that observed within Peyer's patches. In this report we determined a set of parameters that act synergistically to generate up to 15 to 20% mIgA+ cells in vitro. A dual mode of B cell activation is required whereby signaling through CD40 or in response to LPS stimulation must occur in concert with multivalent Ag receptor crosslinking. A complex cytokine requirement is also revealed in that both IL-4 and IL-5 must be present with TGF-beta for high-rate IgA class switching to occur. By contrast, IFN-gamma, a known antagonist of IL-4, strongly suppresses the induction of mIgA+ cells in response to these stimuli. This novel cellular system should serve as a powerful tool for studying the molecular mechanisms that underly the IgA class switch and may provide insight into the physiologic parameters that induce it.
诱导高速率IgA类别转换所需的参数尚不清楚。因此，尽管转化生长因子-β（TGF-β）是IgA类别的转换因子，但在体外，响应TGF-β和各种B细胞激活的个体模式所产生的膜（m）IgA+细胞百分比仅限于总B细胞群体的1%至2%，这一百分比远低于派尔集合淋巴结内观察到的比例。在本报告中，我们确定了一组协同作用的参数，可在体外产生高达15%至20%的mIgA+细胞。需要一种双重模式的B细胞激活，即通过CD40发出的信号或对LPS刺激的响应必须与多价抗原受体交联同时发生。还揭示了一种复杂的细胞因子需求，即IL-4和IL-5必须与TGF-β同时存在，才能发生高速率的IgA类别转换。相比之下，干扰素-γ（IFN-γ）是一种已知的IL-4拮抗剂，它强烈抑制对这些刺激产生的mIgA+细胞的诱导。这种新型细胞系统应成为研究IgA类别转换基础分子机制的有力工具，并可能为诱导该转换的生理参数提供见解。
