Berton M T, Vitetta E S
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
Int Immunol. 1992 Mar;4(3):387-96. doi: 10.1093/intimm/4.3.387.
T cell-dependent B cell activation and the induction of isotype switching require antigen and direct contact with helper T (Th) cells. During activation, B cells can switch from the expression of IgM to that of IgG, IgE or IgA, depending on the lymphokines secreted by the Th cell with which they interact. Studies of lipopolysaccharide (LPS)-activated B cells have suggested that lymphokines regulate isotype switching via a transcriptional mechanism that increases the accessibility of downstream CH genes to a switch recombinase(s). To assess the roles of T cell contact and lymphokines in isotype switching, we have examined the accessibility model for the regulation of isotype switching to IgG1 in the context of cognate interactions between Th cells and normal B cells. We demonstrate that Th2 cells that secrete IL-4 can induce expression of germline gamma 1 transcripts in B cells. The steady-state level of germline gamma 1 transcripts induced by Th2 cells is enhanced as compared with the level induced by IL-4 alone or Il-4 and LPS also alters the relative usage of the germline gamma 1 transcription initiation sites. Enhanced expression of germline gamma 1 transcripts requires direct contact between T and B cells suggesting a role for T cell contact-mediated signals in regulating the accessibility of switch regions.
依赖T细胞的B细胞活化及同种型转换的诱导需要抗原以及与辅助性T（Th）细胞的直接接触。在活化过程中，B细胞可根据与其相互作用的Th细胞分泌的淋巴因子，从表达IgM转换为表达IgG、IgE或IgA。对脂多糖（LPS）活化的B细胞的研究表明，淋巴因子通过一种转录机制调节同种型转换，该机制可增加下游CH基因对一种或多种转换重组酶的可及性。为了评估T细胞接触和淋巴因子在同种型转换中的作用，我们在Th细胞与正常B细胞的同源相互作用背景下，研究了同种型转换至IgG1的调节的可及性模型。我们证明，分泌IL-4的Th2细胞可诱导B细胞中种系γ1转录本的表达。与单独的IL-4或IL-4和LPS诱导的水平相比，Th2细胞诱导的种系γ1转录本的稳态水平有所提高，并且IL-4和LPS还改变了种系γ1转录起始位点的相对使用情况。种系γ1转录本表达的增强需要T细胞与B细胞的直接接触，这表明T细胞接触介导的信号在调节转换区的可及性中发挥作用。
