CD21 augments antigen presentation in immune individuals

?Many infectious agents, in activating the complement system, become covalently linked to the third component of complement, C3. The C3 degradation products, iC3b and C3d, are ligands for CD21. A role for CD21 in antigen processing and presentation has been suggested. The ability of antigennonspecific B cells to present soluble immune complexes was tested. Influenza virus was incubated with serum from immune donors to create complementcontaining complexes. These bound specifically to CD21 on transfected fibroblasts and B cell lines, as measured by flow cytometry. Significant immune complex binding required a threshold level of CD21 expression, suggesting that only those cells with the highest levels of CD21 are likely to participate in the processing of macromolecular antigens. Binding of immune complexes was ablated by inactivation of serum complement. In addition, immunoglobulin in immune serum blocked influenza binding to cells in the absence of complement, implying a minimal role for immunoglobulin-Fcγ receptor interactions in this system. B cells pulsed with complement-influenza complexes elicited an augmented response from a panel of influenza-specific, class Il-restricted T cell clones. Both transformed and resting peripheral blood B cells presented antigen bound by CD21, demonstrating that CD21 ligation is sufficient for B cell antigen presentation. These findings suggest that, in immune individuals, complement-mediated antigen presentation plays a critical role in the development of an appropriate immune response.