Lymphocyte activation by the Fc region of immunoglobulins.
The Fc region of Ig is required for numerous biological effector functions which include: opsonization, anaphylaxis, C fixation, catabolism of the Ig molecule, FcR binding, and immune regulation. To this latter point, the cellular and subcellular events involved in immune regulation by IC and Fc fragments of Ig have been the focus of numerous investigations. Characterization of cyanogen bromide cleavage fragments from a human IgG1 myeloma protein indicates that one biologically-active site is found in residues 335-357 of the CH3 domain of the molecule. Synthesis of the biologically-active region resulted in a peptide, termed p23, which stimulates mouse and human B cells to secrete polyclonal Ig and activates AA metabolic pathways. In contrast to these findings, p23 is unable to induce B cell proliferation or IL-1 secretion from macrophages. Analysis of data obtained with overlapping peptides, based on p23, suggests that the minimal active sequence needed for B cell differentiation is leu-pro-pro-ser-arg (residues 351-355). In contrast, only p23 or p23 minus the carboxyterminal glu356 and glu357 were able to induce PGE release. Release of biologically-active peptides derived from the Fc region of Ig into the cellular microenvironment may form the nucleus of a nonspecific in vivo immunoregulatory network. The specificity of peptide regulatory activities could reside in their effectiveness at high concentrations in the cellular microenvironment. The interaction of Fc region peptides with receptors on B cells, T cells, and macrophages/monocytes could result in a dynamic control of immune reactivity.
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000936:Antigen-Antibody Complex / Q000276:immunology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification
D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids; D007141:Immunoglobulin Fc Fragments; D010446:Peptide Fragments; D016718:Arachidonic Acid