[Advances in the study of long-lived plasma cells]

Long-lived plasma cells (LLPCs) are primarily found in the CD19^-CD38^hiCD138⁺ plasma cell subset in the human bone marrow. They produce antibodies continuously for several years or even decades after initial infection or vaccination, and are essential for durable anti-infective immunity. Compared to short-lived plasma cells, LLPCs express higher levels of surface molecules such as CD27, CD38, CD138, C-X-C chemokine receptor 4 (CXCR4), interleukin 6 receptor (IL-6R), and B-cell maturation antigen (BCMA). However, specific markers for LLPCs have not been identified yet. Currently, transgenic mouse models like Blimp1-CreERT-TdTomato are primarily used for in vivo tracing and functional studies of these cells. The vast majority of LLPCs originate from germinal center-derived plasmablasts. These plasmablasts migrate from the blood to specific survival niches in the bone marrow. Within these niches, cytokines such as a proliferation-inducing ligand (APRIL) and IL-6 are provided to promote LLPC survival. Simultaneously, key transcription factors such as Blimp-1, X-box binding protein 1 (XBP-1), and IRF4 play pivotal roles in the differentiation, maturation, and long-term maintenance of LLPCs by regulating related gene expression, participating in signaling pathway activation, and enabling metabolic adaptation. The early "imprinting" conferred by the germinal center reaction, together with the bone marrow survival niche, promotes the generation of LLPCs. Furthermore, pathogenic LLPCs that persistently produce autoantibodies contribute to the recurrence of autoimmune diseases like rheumatoid arthritis. Consequently, targeted elimination of these cells has emerged as a critical research direction for treating autoimmune disorders.