Perfetti V, Bellotti V, Garini P, Zorzoli I, Rovati B, Marinone M G, Ippoliti G, Merlini G
Department of Internal Medicine, Institute of Clinical Medicine II, University of Pavia, Italy.
Lab Invest. 1994 Dec;71(6):853-61.
AL amyloidosis is characterized by systemic tissue deposition of monoclonal Ig light chains synthesized by a bone marrow plasma cell (PC) clone whose biologic characteristics remain undetermined.
Anti-idiotypic (anti-Id) monoclonal antibodies (MoAbs) were used as specific probes to identify and study amyloidogenic cells in two patients by means of immunofluorescence methods. These MoAbs recognized populations of bone marrow pre-PC, PC, and peripheral blood lymphocytes. To test whether the circulating Id+ lymphocytes were capable of PC differentiation, peripheral blood lymphocytes were incubated with the differentiation-inducing agents, interleukin-3 and interleukin-6 in liquid culture. Preincubation with the anti-Id MoAb and complement was used to inhibit formation of Id+PC in vitro.
The anti-Id MoAb identified three types of cells in the bone marrow with cytoplasmic Ig having the same isotype as the monoclonal component: a) lymphoid cells, that were slightly larger than common peripheral blood lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-, 100% CD10-, 100% mu-chain-); b) lymphoplasmacytoid cells with more abundant cytoplasm and Id+ Ig (CD45RA-, CD45RO-, CD10-, 53% CD38+); 3) mature PC that were very similar to normal PC in morphology and antigenic profile (CD38+, PCA1+, CD56-). A different picture was seen when anti-Id MoAb were used to detect peripheral blood Id+ elements: analysis revealed a population of mature resting surface Ig+ B lymphocytes. Circulating Id+ lymphocytes differentiated in vitro to PC and lymphoplasmacytoid cells that were very similar to those present in the bone marrow. A significant reduction in the number of Id+ PC was obtained after incubation with the anti-Id MoAb and complement.
This study shows that the amyloidogenic cell clone is constituted by at least the following cell populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells and PC) and a subset of peripheral blood post-switched B lymphocytes. The results suggest a relationship among these cells, indicating that circulating Id+ lymphocytes may be the possible precursors of the more differentiated bone marrow population.
AL淀粉样变性的特征是由骨髓浆细胞（PC）克隆合成的单克隆Ig轻链在全身组织中沉积，其生物学特性尚不清楚。
抗独特型（抗Id）单克隆抗体（MoAb）被用作特异性探针，通过免疫荧光方法识别和研究两名患者中的淀粉样变性细胞。这些MoAb识别骨髓前PC、PC和外周血淋巴细胞群体。为了测试循环中的Id +淋巴细胞是否能够分化为PC，将外周血淋巴细胞与分化诱导剂白细胞介素-3和白细胞介素-6在液体培养中孵育。用抗Id MoAb和补体进行预孵育以在体外抑制Id + PC的形成。
抗Id MoAb在骨髓中鉴定出三种类型的细胞，其细胞质Ig具有与单克隆成分相同的同种型：a）淋巴细胞，比普通外周血淋巴细胞稍大（47% CD45RA +，28% CD45R0 +，97% CD38 -，100% CD10 -，100% μ链 -）；b）淋巴浆细胞样细胞，细胞质更丰富且Id + Ig（CD45RA -，CD45RO -，CD10 -，53% CD38 +）；3）成熟PC，其形态和抗原谱与正常PC非常相似（CD38 +，PCA1 +，CD56 -）。当使用抗Id MoAb检测外周血Id +成分时，情况不同：分析显示有一群成熟的静止表面Ig + B淋巴细胞。循环中的Id +淋巴细胞在体外分化为PC和淋巴浆细胞样细胞，与骨髓中的细胞非常相似。用抗Id MoAb和补体孵育后，Id + PC的数量显著减少。
本研究表明，淀粉样变性细胞克隆至少由以下细胞群体组成：一部分骨髓细胞（淋巴细胞、淋巴浆细胞样细胞和PC）和外周血转换后B淋巴细胞的一个亚群。结果表明这些细胞之间存在关系，表明循环中的Id +淋巴细胞可能是分化程度更高的骨髓群体的可能前体。
