Division of Molecular Immunology, Internal Medicine III, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Eur J Immunol. 2021 May;51(5):1089-1109. doi: 10.1002/eji.202048993. Epub 2021 Feb 1.
Long-lived antibody-secreting plasma cells are essential to establish humoral memory against pathogens. While a regulatory transcription factor network has been established in plasma cell differentiation, the regulatory role of miRNAs remains enigmatic. We have recently identified miR-148a as the most abundant miRNA in primary mouse and human plasma cells. To determine whether this plasma cell signature miRNA controls the in vivo development of B cells into long-lived plasma cells, we established mice with genomic, conditional, and inducible deletions of miR-148a. The analysis of miR-148a-deficient mice revealed reduced serum Ig, decreased numbers of newly formed plasmablasts and reduced CD19-negative, CD93-positive long-lived plasma cells. Transcriptome and metabolic analysis revealed an impaired glucose uptake, a reduced oxidative phosphorylation-based energy metabolism, and an altered abundance of homing receptors CXCR3 (increase) and CXCR4 (reduction) in miR-148a-deficient plasma cells. These findings support the role of miR-148a as a positive regulator of the maintenance of long-lived plasma cells.
长寿的抗体分泌浆细胞对于建立针对病原体的体液免疫记忆至关重要。虽然浆细胞分化过程中的调控转录因子网络已经建立，但 miRNA 的调控作用仍然是个谜。我们最近发现 miR-148a 是初级小鼠和人类浆细胞中最丰富的 miRNA。为了确定这种浆细胞特征性 miRNA 是否控制体内 B 细胞向长寿浆细胞的发育，我们建立了基因组、条件和诱导性缺失 miR-148a 的小鼠。对 miR-148a 缺失小鼠的分析表明，血清 Ig 减少，新形成的浆母细胞数量减少，CD19 阴性、CD93 阳性的长寿浆细胞减少。转录组和代谢分析显示，miR-148a 缺失的浆细胞中葡萄糖摄取受损，氧化磷酸化为基础的能量代谢减少，归巢受体 CXCR3（增加）和 CXCR4（减少）的丰度发生改变。这些发现支持了 miR-148a 作为维持长寿浆细胞的正调控因子的作用。
