The effect of synthetic peptides corresponding to Fc sequences in human IgG1 on various steps in the B cell activation pathway.

Abstract

The influence of synthetic peptides comprising sequences in the exposed positions of the Fc region of human IgG 1 was tested on B lymphocyte activation. CH 2 domain peptides having an inhibitory effect on antibody-dependent cellular cytotoxicity, as well as the whole Fc fragment, induced the appearance of the early signs of activation on resting B lymphocytes such as increase in cell volume and HLA-DR antigen expression or leukocyte migration inhibitory factor production. The peptides did not induce proliferation of resting B cells even when B cell growth factor (BCGF)-containing supernatants were added. Exposure to Fc fragment, however, induced a weak proliferation which was significantly enhanced by BCGF. On the other hand, both the Fc fragment and the CH 2 or CH 3 domain peptides enhanced the IgM synthesis of human blood mononuclear cells when a suboptimal dose of pokeweed mitogen was present. This effect was lost when Fc fragment or the peptides were added on the third day of culture. These results suggest that the early steps of B cell activation can be induced by Fc fragment and by small molecular weight Fc peptides, which are potential ligands of Fc receptors. The Fc fragment activates B cells to the state where they respond to BCGF, but the peptides do not possess this activity. Furthermore, both Fc fragment and Fc peptides are able to enhance the IgM synthesis, when accessory cells and the appropriate differentiating factors are present.