O'Connor Brian P, Gleeson Michael W, Noelle Randolph J, Erickson Loren D
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Immunol Rev. 2003 Aug;194:61-76. doi: 10.1034/j.1600-065x.2003.00055.x.
Long-lived humoral immune responses are a hallmark of thymus-dependent immunity. The cellular basis for enduring antibody-mediated immunity is long-lived memory B cells and plasma cells (PCs). Both of these cell populations acquire longevity as a result of antigen-specific, CD40-dependent, cognate interactions with helper T cells within germinal centers (GCs). At the molecular level, defined functional domains of CD40 control the post-GC fate of B cells. PC precursors that emerge from these GC reactions are highly proliferative and terminally differentiate to end-stage cells within the bone marrow (BM). The striking phenotypic similarities between the PC precursors and the putative malignant cell in multiple myeloma (MM) suggests that MM may result from the transformation of PC precursors. Within the domain of autoimmune disease, recent studies have shown that dysregulated migration of PCs to the BM may impact immune homeostasis and the development of lupus. Understanding the processes of normal PC differentiation will provide strategic insights into identifying therapeutic targets for the treatment of differentiated B-cell disorders.
长寿的体液免疫反应是胸腺依赖性免疫的一个标志。持久的抗体介导免疫的细胞基础是长寿记忆B细胞和浆细胞（PCs）。这两种细胞群体由于在生发中心（GCs）内与辅助性T细胞发生抗原特异性、CD40依赖性的同源相互作用而获得长寿特性。在分子水平上，CD40的特定功能域控制着B细胞生发中心后的命运。从这些GC反应中产生的PC前体具有高度增殖性，并在骨髓（BM）内终末分化为终末阶段细胞。PC前体与多发性骨髓瘤（MM）中假定的恶性细胞之间显著的表型相似性表明，MM可能源于PC前体的转化。在自身免疫性疾病领域，最近的研究表明，PCs向BM的迁移失调可能会影响免疫稳态和狼疮的发展。了解正常PC分化过程将为识别分化型B细胞疾病的治疗靶点提供战略见解。
