Phenotypic and functional characterization of normal and malignant terminal B (plasma) cells

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Abstract
A number of antigens (Ags) are expressed on normal and malignant terminal B (plasma) cells, including plasma‐cell, earlier B‐cell, and non‐B cell‐Ags. These Ags, coupled with indirect and dual fluorochrome labelling techniques, permit characterization of normal and malignant in vitro and in vivo terminal B‐cell differentiation. The majority (90%) of B cells within spleen bear B1 and lack PCA‐1 Ags. As B cells differentiate to pokeweed mitogen in vitro, immunoglobulin (Ig) secretion precedes the appearance of cell surface PCA‐1 and plasmacytoid morphology. Dual fluorescence cell sorting permits characterization of in vivo B‐cell differentiation: B1 + PCA‐1 + cells are more “differentiated” since they are more prevalent in lymph node than spleen, exhibit plasmacytoid morphology and maximal Ig secretion, and no longer respond to triggers of B‐cell proliferation; in contrast, B1 + PCA‐1‐ cells are lymphoid in morphology and may respond to triggers of B‐cell proliferation as “resting” B cells. Similar studies of myeloma cells demonstrated that they may also include cells expressing plasma‐cell, earlier B, and non‐B cell Ags. Although they neither proliferated nor secreted Ig in vitro to G/M‐CSF, G‐CSF, M‐CSF, IL‐1, IL‐1B, IL‐2, or IL‐4, proliferation without Ig secretion (Stimulation Index ≥ 3.0) was induced to IL‐6 in 6 of 10 patients (pts); to IL‐3 (2 pts) and to IL‐5 (2 pts). Myeloma cells which proliferated to the greatest extent to IL‐6 have plasmablast morphology and appear to express an earlier B‐cell phenotype (B4±CALLA±B1 + PCA‐1 ±) than those cells which either did not or only weakly responded (B4‐CALLA ‐B1±PCA ‐1±). Phenotypic definition of growth factor‐responsive myeloma cells may both facilitate their biological characterization in vitro and permit enhanced understanding of aberrant B‐cell differentiation in vivo.

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