Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 2022 Jun 21;119(25):e2121260119. doi: 10.1073/pnas.2121260119. Epub 2022 Jun 15.
Antibodies are produced across multiple isotypes with distinct properties that coordinate initial antigen clearance and confer long-term antigen-specific immune protection. Here, we interrogate the molecular programs of isotype-specific murine plasma cells (PC) following helper T cell-dependent immunization and within established steady-state immunity. We developed a single-cell-indexed and targeted molecular strategy to dissect conserved and divergent components of the rapid effector phase of antigen-specific IgM versus inflammation-modulating programs dictated by type 1 IgG2a/b PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC type 2 inhibitory IgG1 and type 1 inflammatory IgG2a/b PC to direct long-term cellular function. In the steady state, two subsets of IgM and separate IgG2b PC programs clearly segregate from splenic type 3 IgA PC programs that emphasize mucosal barrier protection. These diverse isotype-specific molecular pathways of PC differentiation control complementary modules of antigen clearance and immune protection that could be selectively targeted for immunotherapeutic applications and vaccine design.
抗体有多种同种型，具有不同的特性，可协调初始抗原清除并赋予长期的抗原特异性免疫保护。在这里，我们研究了辅助性 T 细胞依赖性免疫接种后和既定稳态免疫中同种型特异性小鼠浆细胞 (PC) 的分子程序。我们开发了一种单细胞索引和靶向分子策略，以剖析抗原特异性 IgM 的快速效应阶段的保守和不同成分，以及由 1 型 IgG2a/b PC 分化决定的炎症调节程序。在抗体亲和力成熟过程中，生发中心 (GC) 周期赋予 GC 后调节 2 型抑制性 IgG1 和 1 型炎症性 IgG2a/b PC 的可分离程序，以指导长期细胞功能。在静息状态下，IgM 的两个亚群和分离的 IgG2b PC 程序与强调粘膜屏障保护的脾脏 3 型 IgA PC 程序明显分开。PC 分化的这些不同同种型特异性分子途径控制抗原清除和免疫保护的互补模块，可针对免疫治疗应用和疫苗设计进行选择性靶向。
