Exosomes Released from Mycoplasma Infected Tumor Cells Activate Inhibitory B Cells

Mycoplasmas cause numerous human diseases and are common opportunistic pathogens in cancer patients and immunocompromised individuals. Mycoplasma infection elicits various host immune responses. Here we demonstrate that mycoplasma-infected tumor cells release exosomes (myco+ exosomes) that specifically activate splenic B cells and induce splenocytes cytokine production. Induction of cytokines, including the proinflammatory IFN-γ and the anti-inflammatory IL-10, was largely dependent on the presence of B cells. B cells were the major IL-10 producers. In splenocytes from B cell deficient μMT mice, induction of IFN-γ+ T cells by myco+ exosomes was greatly increased compared with wild type splenocytes. In addition, anti-CD3-stimulated T cell proliferation was greatly inhibited in the presence of myco+ exosome-treated B cells. Also, anti-CD3-stimulated T cell signaling was impaired by myco+ exosome treatment. Proteomic analysis identified mycoplasma proteins in exosomes that potentially contribute to the effects. Our results demonstrate that mycoplasma-infected tumor cells release exosomes carrying mycoplasma components that preferentially activate B cells, which in turn, are able to inhibit T cell activity. These results suggest that mycoplasmas infecting tumor cells can exploit the exosome pathway to disseminate their own components and modulate the activity of immune cells, in particular, activate B cells with inhibitory activity

The Genealogy of the Labor Hoarding Concept

The modern concept of labor hoarding emerged in early 1960s, and soon became a standard part of mainstream economists' explan ation of the working of labor markets. The concept represents the convergence of three importa nt elements: an empirical fi nding that labor productivity was procyclical; a framing of this fi nding as a "puzzle" or anomaly fo r the basic neoclassical theory of the firm, and a proposed resolu tion of the puzzle based on optimizing behavior of the firm in the presence of costs of hiring, firing, and training workers. Th is paper recounts the history of each of these elements, and how they were woven together into the labor hoarding concept. Each history involves people associated with various research traditions and motivated by an array of questions, many of which were unrelated to the qu estions that the modern labor hoarding concept was ultimately created to address