No abstract

B cells have a critical role in the initiation and acceleration of autoimmune diseases, especially those mediated by autoantibodies. In the peripheral lymphoid system, mature B cells are activated by self or/and foreign antigens and signals from helper T cells for differentiating into either memory B cells or antibody-producing plasma cells. Accumulating evidence has shown that epigenetic regulations modulate somatic hypermutation and class switch DNA recombination during B-cell activation and differentiation. Any abnormalities in these complex regulatory processes may contribute to aberrant antibody production, resulting in autoimmune pathogenesis such as systemic lupus erythematosus. Newly generated knowledge from advanced modern technologies such as next-generation sequencing, single-cell sequencing and DNA methylation sequencing has enabled us to better understand B-cell biology and its role in autoimmune development. Thus this review aims to summarize current research progress in epigenetic modifications contributing to B-cell activation and differentiation, especially under autoimmune conditions such as lupus, rheumatoid arthritis and type 1 diabetes.

Programmed death-ligand 1 (PD-L1) is thought to play a critical role in immune escape by cancer, but whether PD-L1 expression can influence prognosis of patients with solid tumors is controversial. Therefore, we meta-analyzed available data on whether PD-L1 expression correlates with overall survival (OS) in such patients. PubMed, EMBASE and other databases were systematically searched for cohort or case-control studies examining the possible correlation between PD-L1 expression and OS of patients with solid tumors. OS was compared between patients positive or negative for PD-L1 expression using scatter plots, and subgroup analyses were performed based on tumor type and patient characteristics. Data from 59 studies involving 20,004 patients with solid tumors were meta-analyzed. The median percentage of tumors positive for PD-L1 was 30.1%. OS was significantly lower in PD-L1-positive patients than in PD-L1-negative patients at 1 year (P = 0.039), 3 years (P < 0.001) and 5 years (P < 0.001). The risk ratios of OS (and associated 95% confidence intervals) were 2.02 (1.56-2.60) at 1 year, 1.57 (1.34-1.83) at 3 years and 1.43 (1.24-1.64) at 5 years. Similar results were obtained in subgroup analyses based on patient ethnicity or tumor type. The available evidence suggests that PD-L1 expression negatively affects the prognosis of patients with solid tumors. PD-L1 might serve as an efficient prognostic indicator in solid tumor and may represent the important new therapeutic target.