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The Human B Cell Response to IL-13 Is Dependent on Cellular Phenotype as Well as Mode of Activation¹

Dwayne Ford^*, Catherine Sheehan^*, Christopher Girasole^*, Rory Priester^*, Nicola Kouttab^*, John Tigges^*, Thomas C. King, Andrea Luciani^*, John W. Morgan^* and Abby L. Maizel^2,*

^* Department of Pathology, Roger Williams Medical Center, Boston University School of Medicine, Boston, MA 02118; and Lifespan Health Care System, Brown University School of Medicine, Providence, RI 02908

Normal mature quiescent human B lymphocytes, isolated as a function of buoyant density, require activation for up-regulation of IL-13R constituents. Cell activation through a combination of surface Ig and CD40 receptor ligation leads to the most substantial message production for IL-13R1. Functional consequences of this receptor variation, in initially quiescent cells, includes demonstrable effects on cellular proliferation in response to ligand exposure. Variations in the method of surface activation, with particular emphasis on the CD40 receptor, reveals that immobilized CD40 ligand may be sufficient, in and of itself, to up-regulate IL-13R1, which may bear significance for B-lymphocyte bystander proliferation. Regulation of the IL-13R1 protein and message also differs as a function of cellular phenotype. Although values are greater in memory than naive B cells, as they are initially isolated from extirpated tonsils, variations in the magnitude of message and protein, as a function of surface stimulation, are more substantial in the naive subset. The magnitude of variation in message production in naive cells is associated with a more vigorous proliferative response to IL-13 than seen in memory lymphocytes. The cellular response to IL-13, as a function of activation and phenotype, is the converse of that demonstrated for IL-2. Evaluation of proliferation, receptor message, ligand binding protein production, and the response to putatively synergistic cytokines reveals that IL-2 is the predominant lymphokine utilized by memory cells. This is in contradistinction to IL-13, which along with IL-4, are the predominant moieties for naive lymphocytes.

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