Jensen G S, Andrews E J, Mant M J, Vergidis R, Ledbetter J A, Pilarski L M
Department of Immunology, University of Alberta, Edmonton, Canada.
Am J Hematol. 1991 May;37(1):20-30. doi: 10.1002/ajh.2830370106.
Waldenstrom's macroglobulinemia (WM) has been hypothesized to be a pleomorphic B-cell malignancy with persistent maturation towards plasma cells in all lymphoid tissue. This proposal is based on detection of a heterogeneous density of monoclonal Ig on peripheral blood B-cells in patients with WM. We now present data derived from 2- and 3-color immunofluorescence and flow cytometric analysis that strongly supports this hypothesis. Abnormally high numbers of B lineage cells, defined by expression of CD19, CD20, and CD24, were found among peripheral blood mononuclear cells (PBMC). These B-cells are monoclonal as defined by light chain expression and by the existence of rearranged Ig genes (Southern blot analysis), although they exhibit heterogeneity in the density of surface light chain. Unlike normal PBMC B-cells, the monoclonal B-cells bear CD5 and CD10 (CALLA), express adhesion and adhesion-related molecules (CD11b, CD9), and appear to be actively differentiating during the course of the disease, based on the pattern of CD45 isoform expression. At any given point in time, the population of monoclonal B-cells is heterogeneous in differentiation stage based on transitions in the expression of CD45 isoforms from expression of CD45RA, the high molecular mass isoforms of CD45, to the low molecular mass isoform CD45R0 which appears only on very late stage B-cells and early plasma cells. For one patient, analysis of CD45 isoform expression over 2 years showed that the monoclonal B-cell population as a whole progressed towards terminal differentiation as defined by loss of CD45RA and acquisition of CD45R0. This indicates a continuously differentiating lineage of an unusual B-cell phenotype, and/or malignant transformation of a distinct lineage of B-cells in WM.
华氏巨球蛋白血症（WM）被推测为一种多形性B细胞恶性肿瘤，在所有淋巴组织中持续向浆细胞成熟。这一观点基于对WM患者外周血B细胞上单克隆Ig异质性密度的检测。我们现在展示来自双色和三色免疫荧光以及流式细胞术分析的数据，这些数据有力地支持了这一假设。在外周血单核细胞（PBMC）中发现了数量异常高的B淋巴细胞系细胞，这些细胞通过CD19、CD20和CD24的表达来定义。根据轻链表达以及重排Ig基因的存在（Southern印迹分析），这些B细胞是单克隆的，尽管它们在表面轻链密度上表现出异质性。与正常PBMC B细胞不同，单克隆B细胞带有CD5和CD10（CALLA），表达黏附分子和黏附相关分子（CD11b、CD9），并且基于CD45异构体的表达模式，在疾病过程中似乎正在积极分化。在任何给定时间点，基于CD45异构体表达从高分子量异构体CD45RA向仅出现在非常晚期B细胞和早期浆细胞上的低分子量异构体CD45R0的转变，单克隆B细胞群体在分化阶段是异质的。对于一名患者，对2年期间CD45异构体表达的分析表明，整个单克隆B细胞群体朝着终末分化发展，表现为CD45RA的丢失和CD45R0的获得。这表明WM中存在一种异常B细胞表型的持续分化谱系，和/或一种独特B细胞谱系的恶性转化。
