Yang Jessica A, Tubo Noah J, Gearhart Micah D, Bardwell Vivian J, Jenkins Marc K
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455; and.
Developmental Biology Center, Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455; and University of Minnesota Masonic Cancer Center, Minneapolis, MN 55455.
J Immunol. 2015 Jun 15;194(12):5604-8. doi: 10.4049/jimmunol.1500201. Epub 2015 May 11.
CD4(+) germinal center (GC)-T follicular helper (Tfh) cells help B cells become long-lived plasma cells and memory cells. The transcriptional repressor Bcl6 plays a key role in GC-Tfh formation by inhibiting the expression of genes that promote differentiation into other lineages. We determined whether BCOR, a component of a Polycomb repressive complex that interacts with the Bcl6 BTB domain, influences GC-Tfh differentiation. T cell-targeted BCOR deficiency led to a substantial loss of peptide:MHC class II-specific GC-Tfh cells following Listeria monocytogenes infection and a 2-fold decrease following immunization with a peptide in CFA. The reduction in GC-Tfh cells was associated with diminished plasma cell and GC B cell formation. Thus, T cell-expressed BCOR is critical for optimal GC-Tfh cell differentiation and humoral immunity.
CD4(+)生发中心(GC)-T滤泡辅助(Tfh)细胞帮助B细胞成为长寿浆细胞和记忆细胞。转录抑制因子Bcl6通过抑制促进向其他谱系分化的基因表达,在GC-Tfh形成中起关键作用。我们确定了BCOR(一种与Bcl6 BTB结构域相互作用的多梳抑制复合物的组成部分)是否影响GC-Tfh分化。靶向T细胞的BCOR缺陷导致单核细胞增生李斯特菌感染后肽:MHC II类特异性GC-Tfh细胞大量减少,以及在CFA中用肽免疫后减少两倍。GC-Tfh细胞的减少与浆细胞和GC B细胞形成减少有关。因此,T细胞表达的BCOR对于最佳的GC-Tfh细胞分化和体液免疫至关重要。