Abstract:
Autophagy is a regulated intracellular catabolic process by which invading pathogens, damaged organelles, aggregated proteins, and other macromolecules are degraded in lysosomes. It has been widely appreciated that autophagic activity plays an important role in regulating the development, fate determination, and function of cells in the immune system, including B lymphocytes. Autophagy encompasses several distinct pathways that have been linked to B cell homeostasis and function. While B cell presentation of major histocompatibility complex (MHC) class II-restricted cytosolic antigens to T cells involves both macroautophagy and chaperone-mediated autophagy (CMA), plasma cells and memory B cells mainly rely on macroautophagy for their survival. Emerging evidence indicates that core autophagy factors also participate in processes related to yet clearly distinct from classical autophagy. These autophagy-related pathways, referred to as noncanonical autophagy or conjugation of ATG8 to single membranes (CASM), contribute to B cell homeostasis and functions, including MHC class II-restricted antigen presentation to T cells, germinal center formation, plasma cell differentiation, and recall responses. Dysregulation of B cell autophagy has been identified in several autoimmune and autoinflammatory diseases such as systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. In this review, we discuss recent advances in understanding the role of canonical and noncanonical autophagy in B cells, including B cell development and maturation, antigen processing and presentation, pathogen-specific antibody responses, cytokine secretion, and autoimmunity. Unraveling the molecular mechanisms of canonical and noncanonical autophagy in B cells will improve our understanding of B cell biology, with implications for the development of autophagy-based immunotherapies.
摘要:
自噬是一种受调节的细胞内分解代谢过程,受损的细胞器,聚集的蛋白质,和其他大分子在溶酶体中降解。自噬活动在调节发育中起着重要作用,命运的决定,和免疫系统中细胞的功能,包括B淋巴细胞。自噬包括几种与B细胞稳态和功能相关的不同途径。虽然B细胞向T细胞呈递主要组织相容性复合物(MHC)II类限制性胞质抗原涉及巨自噬和伴侣介导的自噬(CMA),浆细胞和记忆B细胞主要依靠巨自噬生存。新的证据表明,核心自噬因子也参与与经典自噬相关的过程,但与经典自噬明显不同。这些自噬相关途径,称为非规范自噬或ATG8与单膜(CASM)的缀合,有助于B细胞稳态和功能,包括MHCII类限制性抗原呈递给T细胞,生发中心形成,浆细胞分化,和回忆回应。B细胞自噬的失调已经在一些自身免疫和自身炎性疾病如系统性红斑狼疮中被发现,类风湿性关节炎,和炎症性肠病.在这次审查中,我们讨论了在理解规范和非规范自噬在B细胞中的作用方面的最新进展,包括B细胞发育和成熟,抗原加工和呈递,病原体特异性抗体反应,细胞因子分泌,和自身免疫。解开B细胞中规范和非规范自噬的分子机制将提高我们对B细胞生物学的理解。对基于自噬的免疫疗法的发展具有重要意义。