CONTROL OF THE IL-2 RESPONSIVENESS OF B-LYMPHOCYTES BY IL-2 AND IL-4

A two-step culture system was used to analyze the parameters involved in the acquisition of IL-2 responsiveness by murine B cells. In the first culture, unstimulated, or resting, B cells prepared from spleen of naive animals were challenged during 48 h with IL-2, IL-4, anti-mu, anti-mu + IL-2, anti-mu + IL-4, or anti-mu + IL-2 + IL-4. In a second culture, IL-2 responsiveness was followed by measuring either the cell proliferation or the Ig production. It was found that only B cells stimulated by anti-mu + IL-2 were able to respond. The expression of three chains of the IL-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) was studied by FACS. IL-2R beta and IL-2R gamma were found to be expressed constitutively on resting B cells. IL-2R alpha was induced by anti-mu and anti-mu + IL-2 treatment. Although B cells treated by anti-mu alone are not able to respond to IL-2, they do express an IL-2 binding capacity comparable with B cells treated by anti-mu + IL-2. This paradoxical result suggests that IL-2 has a direct influence on the acquisition of the IL-2 responsiveness. IL-4 exerts a negative effect on the IL-2 response. At the molecular level, IL-4 was found to reduce selectively the IL-2R beta expression at the B cell surface. This effect was confirmed by Northern blot analysis. Maximum expression of the IL-2R beta mRNA is obtained after anti-mu + IL-2 treatment. In the presence of IL-4, expression of the IL-2R beta mRNA is greatly reduced.