Lack of induced co-stimulation as a result of complement receptor 2 (CR2) ligation on mouse splenic B cells.

B cells act as efficient antigen-presenting cells if they acquire antigen via membrane-bound Ig [termed the B cell receptor (BCR)]. Ligation of the BCR leads to antigen internalization, processing and presentation to CD4+ T cells in association with MHC class II molecules. Ligation of the BCR also leads to the generation of activation signals. One short-term consequence of this is the up-regulation of co-stimulatory molecule expression by the B cell, allowing full T cell activation. Other antigen receptors expressed by B cells can also mediate efficient antigen presentation to CD4+ T cells. Ligating one such receptor, complement receptor 2 (CR2), has also been described to induce co-stimulatory molecule expression. If correct, this may have serious consequences for ensuring the specificity of the resultant B cell response. We have therefore investigated the effects of ligating both the BCR and CR2 independently of each other, as well as with reagents to cross-link the two receptors, in order to clarify these findings. In contrast to the effects seen upon BCR ligation, we find no evidence for co-stimulatory molecule up-regulation following CR2 ligation. As antigen presentation in the absence of co-stimulation may lead to the induction of tolerogenic or regulatory signals being delivered to T cell populations, these findings imply that the role of CR2 in B cell-mediated antigen presentation is different from that of the BCR.