Aungier Susan R, Ohmori Hitoshi, Clinton Michael, Mabbott Neil A
The Roslin Institute and R(D)SVS, University of Edinburgh, Midlothian, UK.
Immunology. 2015 Jan;144(1):34-44. doi: 10.1111/imm.12342.
Follicular dendritic cells (FDC) are important stromal cells within the B-cell follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and retain native antigens on their surfaces in the form of immune complexes that they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non-coding RNAs that are approximately 18-25 nucleotides in length that regulate gene expression at the post-transcriptional level by repressing the translation of target genes. In the current study, in vivo and in vitro systems were used to identify microRNAs that were potentially expressed by FDC. Constitutive lymphotoxin-β receptor (LTβR) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de-differentiation of spleen FDC that accompanied LTβR-blockade, coincided with a significant decrease in the expression of mmu-miR-100-5p, mmu-miR-138-5p and mmu-miR-2137. These microRNAs were shown to be expressed in the FDC-like cell line, FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and promoting high-affinity antibody responses, so it is plausible that mmu-miR-100-5p may help to regulate the expression of these genes during GC reactions.
滤泡树突状细胞（FDC）是次级淋巴组织的B细胞滤泡和生发中心（GC）内重要的基质细胞。FDC以免疫复合物的形式在其表面捕获并保留天然抗原，然后将这些抗原呈递给B细胞，以便选择那些具有最高抗原亲和力的细胞。微小RNA是长度约为18 - 25个核苷酸的短链非编码RNA，它们通过抑制靶基因的翻译在转录后水平调节基因表达。在本研究中，利用体内和体外系统来鉴定可能由FDC表达的微小RNA。维持FDC的分化状态需要组成性淋巴毒素-β受体（LTβR）刺激。我们发现，伴随LTβR阻断的脾脏FDC快速去分化，与mmu-miR-100-5p、mmu-miR-138-5p和mmu-miR-2137表达的显著降低同时发生。这些微小RNA在FDC样细胞系FL-YB中表达，特异性抑制mmu-miR-100-5p可显著增强该细胞系中Il6、Ptgs1/2和Tlr4 mRNA的表达。FDC对Il6、Ptgs1/2和Tlr4的表达在调节生发中心大小和促进高亲和力抗体反应中起重要作用，因此mmu-miR-100-5p可能在生发中心反应期间有助于调节这些基因的表达，这是合理的。
