Perugino Cory A, Liu Hang, Feldman Jared, Marbourg Jess, Guy Thomas V, Hui Anson, Ingram Nicole, Liebaert Julian, Chaudhary Neha, Tao Weiyang, Jacob-Dolan Catherine, Hauser Blake M, Mian Zayd, Nathan Anusha, Zhao Zezhou, Kaseke Clarety, Tano-Menka Rhoda, Getz Matthew A, Senjobe Fernando, Berrios Cristhian, Ofoman Onosereme, Manickas-Hill Zachary, Wesemann Duane R, Lemieux Jacob E, Goldberg Marcia B, Nündel Kerstin, Moormann Ann, Marshak-Rothstein Ann, Larocque Regina C, Ryan Edward T, Iafrate John A, Lingwood Daniel, Gaiha Gaurav, Charles Richelle, Balazs Alejandro B, Pandit Aridaman, Naranbhai Vivek, Schmidt Aaaron G, Pillai Shiv
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Cell Rep. 2025 Apr 22;44(4):115472. doi: 10.1016/j.celrep.2025.115472. Epub 2025 Apr 1.
Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized in terms of durability. The relative durability of eight non-overlapping human B cell sub-populations covering 100% of all human class-switched B cells was interrogated. Only two long-lived B cell populations persisted in the relative absence of antigen. In addition to canonical germinal center-derived switched-memory B cells with an IgDCD27CXCR5 phenotype, a second, non-canonical, but distinct memory population of IgDCD27CXCR5 DN1 B cells was also durable, exhibited a unique TP63-linked transcriptional and anti-apoptotic signature, had low levels of somatic hypermutation, but was more clonally expanded than canonical switched-memory B cells. DN1 B cells likely evolved to preserve immunological breadth and may represent the human counterparts of rodent extrafollicular memory B cells that, unlike canonical memory B cells, can enter germinal centers and facilitate B cell and antibody evolution.
记忆淋巴细胞是在没有抗原的情况下仍能持久存在的长寿细胞，但很少有人类B细胞亚群在耐久性方面得到表征。我们研究了涵盖所有人类类别转换B细胞100%的八个不重叠人类B细胞亚群的相对耐久性。在相对缺乏抗原的情况下，只有两个长寿B细胞群体持续存在。除了具有IgD-CD27-CXCR5表型的典型生发中心来源的转换记忆B细胞外，第二种非典型但独特的IgD-CD27-CXCR5 DN1 B细胞记忆群体也具有耐久性，表现出独特的与TP63相关的转录和抗凋亡特征，体细胞超突变水平较低，但比典型转换记忆B细胞具有更多的克隆扩增。DN1 B细胞可能进化以保持免疫广度，并且可能代表啮齿动物滤泡外记忆B细胞的人类对应物，与典型记忆B细胞不同，后者可以进入生发中心并促进B细胞和抗体的进化。
