After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC. Follicular dendritic cells (FDC) are thought to play a pivotal role in the initiation and maintenance of secondary antibody responses. FDC operate in germinal centers (GC) of lymphoid follicles, where they form a three-dimensional network. Antigens complexed with immunoglobulins and complement fragments are trapped on the surface of FDC in form of immunecomplex-coated bodies or “iccosomes” that contribute to B-cell maturation and B-cell memory (24). FDC express substantial quantities of complement receptor 1 (CR1; CD35) and CR2, in addition to lesser amounts of CR3 (CD11b/CD18) (21). This unique pattern of CR expression allows FDC to interact with all complement C3 fragments: with C3b through CR1, with iC3b through CR2 or CR3, and with C3d via CR2. In the course of human immunodeficiency virus type 1
