Haque Shabirul, Diamond Betty
Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, New York, 11030, USA.
Mol Med. 2025 Jan 29;31(1):28. doi: 10.1186/s10020-025-01068-x.
The process of B cell activation and plasma cell (PC) formation involves morphological, transcriptional, and metabolic changes in the B cell. Blocking or reducing PC differentiation is one approach to treat autoimmune diseases that are characterized by the presence of pathogenic autoantibodies. Recent studies have suggested the potential of myricetin, a natural flavonoid with anti-inflammatory and antioxidant properties, to block or reduce PC differentiation.
Primary human B cells were purified by using a human B cell isolation kit. B cell subsets such as IgG memory B cells, marginal zone B cells (MZ B cells), and naive B cells were isolated by flow cytometry and activated to induce PC differentiation. Quantification of PCs (CD27 + + , CD38 +) was obtained by flow cytometry. The expression of mRNA was measured by qPCR. Ig secretion in culture supernatant was measured by ELISA.
Myricetin treatment significantly reduced PC differentiation in primary human B cells and all B cell subsets. Myricetin exposure reduced Ig production both IgM and IgG, in culture supernatants at day 5. Myricetin treatment led to augmented BACH2 expression and reduced IRF4, BLIMP1, and XBP1 expression compared to control cultures.
Myricetin treatment reduced PC differentiation and Ig secretion by primary human B cells. Targeting B cells in this way may be a therapeutic approach for some autoimmune diseases.
B细胞激活和浆细胞(PC)形成过程涉及B细胞的形态、转录和代谢变化。阻断或减少PC分化是治疗以致病性自身抗体存在为特征的自身免疫性疾病的一种方法。最近的研究表明,杨梅素这种具有抗炎和抗氧化特性的天然黄酮类化合物,有可能阻断或减少PC分化。
使用人B细胞分离试剂盒纯化原代人B细胞。通过流式细胞术分离IgG记忆B细胞、边缘区B细胞(MZ B细胞)和幼稚B细胞等B细胞亚群,并激活以诱导PC分化。通过流式细胞术对PC(CD27 ++、CD38 +)进行定量。通过qPCR测量mRNA的表达。通过ELISA测量培养上清液中的Ig分泌。
杨梅素处理显著降低了原代人B细胞和所有B细胞亚群中的PC分化。在第5天,杨梅素处理降低了培养上清液中IgM和IgG的Ig产生。与对照培养相比,杨梅素处理导致BACH2表达增加,IRF4、BLIMP1和XBP1表达降低。
杨梅素处理减少了原代人B细胞的PC分化和Ig分泌。以这种方式靶向B细胞可能是治疗某些自身免疫性疾病的一种方法。