Low Levels of IFN-γ Down-regulate the Integrin-dependent Adhesion of B Cells by Activating a Pathway That Interferes with Cytoskeleton Rearrangement

Abstract

In order to fully mature and participate in the humoral immune response, immature B cells must first migrate into specific areas in the spleen where they differentiate into mature cells. However, before their maturation in the spleen, immature B cells must be excluded from non-splenic secondary lymphoid organs where any antigen encounter would lead to the death of the cells because of the negative selection process. We have recently shown that immature B cells can actively exclude themselves from antigen-enriched sites by down-regulating their integrin-mediated adhesion in a process mediated by interferon-γ (IFN-γ). In this study, we followed the pathway by which IFN-γ regulates the homing of B cells. We show here that the inhibitory signal of IFN-γ is transmitted through the IFN-γ receptor whose engagement leads to the activation of PI3K. This PI3K activation subsequently leads to the inhibition of PKCα phosphorylation and cytoskeleton rearrangement required for promoting integrin-mediated adhesion and migration of B cells.