Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Front Immunol. 2019 Apr 24;10:852. doi: 10.3389/fimmu.2019.00852. eCollection 2019.
Malaria is a deadly infectious disease associated with fundamental changes in the composition of the memory B cell (MBC) compartment, most notably a large expansion of T-bet MBCs, termed atypical MBCs. However, we know little about the precursors of atypical MBCs and the conditions that drive their differentiation. We compared the responses of human tonsil naïve B cells, MBCs, and germinal center B cells to a variety of stimulatory conditions. We determined that prolonged antigen presentation in the presence of CpG and IFN-γ induced maximal expression of T-bet and other phenotypic markers of malaria-associated atypical MBCs primarily in naïve B cells . Importantly T-bet naïve-derived B cells resembled atypical MBCs in their hypo-responsiveness to signaling through their B cell receptors. Thus, naïve B cells can be induced to differentiate into phenotypically and functionally atypical-like MBCs under conditions that may prevail in chronic infectious diseases .
疟疾是一种致命的传染病，与记忆 B 细胞（MBC）组成的根本变化有关，特别是 T 细胞结合因子（T-bet）MBC 的大量扩张，称为非典型 MBC。然而，我们对非典型 MBC 的前体以及驱动其分化的条件知之甚少。我们比较了人类扁桃体幼稚 B 细胞、MBC 和生发中心 B 细胞对各种刺激条件的反应。我们确定，在 CpG 和 IFN-γ存在的情况下，延长抗原呈递会诱导 T-bet 和其他与疟疾相关的非典型 MBC 的表型标志物的最大表达，主要发生在幼稚 B 细胞中。重要的是，T-bet 幼稚衍生的 B 细胞在其 B 细胞受体信号转导的低反应性方面类似于非典型 MBC。因此，在慢性传染病中可能存在的条件下，幼稚 B 细胞可被诱导分化为表型和功能上类似非典型的 MBC。
