Department of Microbiology and Immunology, Upstate Medical University, Syracuse, NY 13210, USA.
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, NY 13210, USA.
Cell Rep. 2018 Jul 24;24(4):824-837.e3. doi: 10.1016/j.celrep.2018.06.074.
Immunoglobulin M (IgM) memory cells undergo differentiation in germinal centers following antigen challenge, but the full effector cell potential of these cells is unknown. We monitored the differentiation of enhanced yellow fluorescent protein (eYFP)-labeled CD11c and CD11c T-bet IgM memory cells after their transfer into naive recipient mice. Following challenge infection, many memory cells differentiated into IgM-producing plasmablasts. Other donor B cells entered germinal centers, downregulated CD11c, underwent class switch recombination, and became switched memory cells. Yet other donor cells were maintained as IgM memory cells, and these IgM memory cells retained their multi-lineage potential following serial transfer. These findings were corroborated at the molecular level using immune repertoire analyses. Thus, IgM memory cells can differentiate into all effector B cell lineages and undergo self-renewal, properties that are characteristic of stem cells. We propose that these memory cells exist to provide long-term multi-functional immunity and act primarily to maintain the production of protective antibodies.
免疫球蛋白 M（IgM）记忆细胞在抗原刺激后于生发中心发生分化，但这些细胞的全部效应细胞潜能尚不清楚。我们在将增强型黄色荧光蛋白（eYFP）标记的 CD11c 和 CD11c T-bet IgM 记忆细胞转移到 naive 受体小鼠后，监测了它们的分化情况。在受到挑战感染后，许多记忆细胞分化为 IgM 产生的浆母细胞。其他供体 B 细胞进入生发中心，下调 CD11c，经历类别转换重组，并成为转换记忆细胞。然而，其他供体细胞保持为 IgM 记忆细胞，并且这些 IgM 记忆细胞在连续转移后保持其多谱系潜能。这些发现通过免疫受体库分析在分子水平上得到了证实。因此，IgM 记忆细胞可以分化为所有效应 B 细胞谱系并进行自我更新，这些特性是干细胞的特征。我们提出，这些记忆细胞的存在是为了提供长期的多功能免疫，并主要作用是维持保护性抗体的产生。
