Positive and negative regulation of Thy-1 expression on B lymphocytes by IL-4

Expression of the Thy-1 membrane antigen is generally confined to thymocytes and T lymphocytes, but its expression on B lymphocytes can be induced by culture with the lymphokine IL-4. IL-4 was first reported as a soluble factor capable of participating in the activation of B cells. However, it has been shown that the proliferative response of B cells to IL-4 is dependent upon both their stage of differentiation and their prior exposure to other activating signals--under some conditions, IL-4 can inhibit B cell functions. The present study was designed to determine whether IL-4 signaling induces Thy-1 expression on all B lymphocytes, or whether this induction is dependent upon IL-4-mediated activation. We examined the role of IL-4 in regulating both mRNA and protein levels of Thy-1 in three mouse B cell lines with distinct growth responses to IL-4. IL-4 was required for Thy-1 expression in cells which were dependent upon IL-4 for continuous growth in culture but markedly decreased Thy-1 expression in cells which are growth-inhibited by IL-4. In a mutant subclone of the latter cells in which IL-4 signaling does not cause growth inhibition, IL-4 did not affect Thy-1 expression. The regulation of Thy-1 expression by IL-4 is manifest at the level of Thy-1 mRNA. Thus, IL-4 can both positively and negatively influence B cell expression of Thy-1, depending on the growth response of the cells to IL-4.