ABSTRACT Human activated CD4+ T cells have been shown to provide helper signals to resting B cells to express CD25 and CD71 as well as exert suppressive influences on the proliferation and differentiation of activated B cells. It has been also demonstrated that activated T cells provide helper signals to resting B cells through direct cellular interactions, mainly mediated by CD40-CD40 ligand (CD40L) interactions. It was also disclosed that the suppression of human B cell responses by activated CD4+ T cells requires direct cellular interactions between B cells and T cells. Human B cells express functional Fas receptor on activation through CD40 ligation and become sensitive to Fas mediated apoptosis. In fact, apoptosis indicing anti-Fas mAb suppresses the Ig production of B cells activated through CD40 ligation. However, neither neutralizing anti-Fas mAb nor anti-FasL mAb reversed the suppressive influences of anti-CD3-activated CD4+ T cells on B cell responses, suggesting that the interactions other than those mediated through Fas and FasL might also play a critical role in the suppression of B cell responses by activated human T cells. Apart from the positive impact on B cell responses, there have been several lines of evidence that CD40-CD40L interactions deliver negative signals to human B cell responses. Accordingly, our recent studies have clearly shown that anti-CD40L almost completely reversed the suppressive influences of anti-CD3-activated CD4+ T cells on the Ig production on human peripheral blood B cells, thus supporting the hypothesis that CD40-CD40L interactions play a critical role in the suppression of B cell responses by activated CD4+ T cells. Collectively, these observation lead to a conclusion that CD40-CD40L interactions between B cells and CD4+ T cells are bidirectional and that the state of activation of B cells and the extent of CD40 engagement on B cells are important in determining the direction of signals.
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