Claireaux Mathieu, Elias George, Kerster Gius, Kuijper Lisan H, Duurland Mariël C, Paul Alberta G A, Burger Judith A, Poniman Meliawati, Olijhoek Wouter, de Jong Nina, de Jongh Rivka, Wynberg Elke, van Willigen Hugo D G, Prins Maria, De Bree Godelieve J, de Jong Menno D, Kuijpers Taco W, Eftimov Filip, van der Schoot C Ellen, Rispens Theo, Garcia-Vallejo Juan J, Ten Brinke Anja, van Gils Marit J, van Ham S Marieke
Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Amsterdam Institute for Immunology and Infectious diseases, Amsterdam, Netherlands.
Sci Adv. 2025 Feb 21;11(8):eado1331. doi: 10.1126/sciadv.ado1331. Epub 2025 Feb 19.
Improving our understanding of B cell transition to memory B cells (MBCs) and antibody-secreting cells (ASCs) is crucial for clinical monitoring and vaccine strategies. To explore these dynamics, we compared prepandemic antigen responses (influenza hemagglutinin, respiratory syncytial virus fusion glycoprotein, and tetanus toxoid) with recently encountered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen responses in convalescent COVID-19 patients using spectral flow cytometry. Our analysis revealed the CD43+CD71+IgG+ activated B cell subset, highly enriched for SARS-CoV-2 specificities, as a juncture for ASC and MBC differentiation, with CD86+ phenotypically similar to ASCs and CD86- to IgG+ MBCs. Moreover, subpopulations within IgG+ MBCs were further identified based on CD73 and CD24 expression. Activated MBCs (CD73-/CD24lo) were predominantly SARS-CoV-2-specific, while resting MBCs (CD73+/CD24hi) recognized prepandemic antigens. A CD95- subcluster within resting MBCs accounted for over 40% of prepandemic-specific cells, indicating long-lasting memory. These findings advance our understanding of IgG+ MBC and ASC development stages, shedding light on the decision-making process guiding their differentiation.
提高我们对B细胞向记忆B细胞（MBC）和抗体分泌细胞（ASC）转变的理解，对于临床监测和疫苗策略至关重要。为了探究这些动态变化，我们使用光谱流式细胞术，比较了康复期COVID-19患者中疫情前的抗原反应（流感血凝素、呼吸道合胞病毒融合糖蛋白和破伤风类毒素）与近期遇到的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗原反应。我们的分析揭示，CD43+CD71+IgG+活化B细胞亚群高度富集SARS-CoV-2特异性，是ASC和MBC分化的一个关键节点，其中CD86+在表型上与ASC相似，而CD86-与IgG+ MBC相似。此外，基于CD73和CD24的表达进一步鉴定了IgG+ MBC内的亚群。活化的MBC（CD73-/CD24lo）主要针对SARS-CoV-2特异性，而静止的MBC（CD73+/CD24hi）识别疫情前的抗原。静止MBC内的一个CD95-亚群占疫情前特异性细胞的40%以上，表明存在持久记忆。这些发现推进了我们对IgG+ MBC和ASC发育阶段的理解，为指导它们分化的决策过程提供了线索。
