Endocytosis and Recycling of Immune Complexes by Follicular Dendritic Cells Enhances B Cell Antigen Binding and Activation

• Visualizing direct immune complex transfer from noncognate B cells to FDCs in vivo
• Uptake of immune complexes from noncognate B cells by FDCs is actin dependent
• Immune complexes cycling to the FDC surface are displayed for B cell acquisition
• In vivo, FDCs retain immune complexes in a cycling compartment for at least 16 days

SummaryStromal-derived follicular dendritic cells (FDCs) are a major reservoir for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate. A long-standing question is how FDCs retain antigen in its native form for extended periods and how they display it to specific B cells. Here we found that FDCs acquired complement-coated immune complexes (ICs) from noncognate B cells via complement receptors 1 and 2 (CD35 and CD21, respectively) and rapidly internalized them by an actin-dependent pathway. ICs were retained intact within a nondegradative cycling compartment and were displayed periodically on the cell surface where they were accessible to antigen-specific B cells. This would explain how antigens are protected from damage and retained over long periods of time, while remaining accessible for B cells.

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