Visualizing B cell capture of cognate antigen from follicular dendritic cells

Abstract

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell.

Cocapture of cognate and bystander antigens can activate autoreactive B cells

“…Antigen capture from cell membranes differs significantly from capture of soluble antigen: Membrane-bound antigens are multivalent, increasing the binding avidity in comparison with a monovalent antigen in solution (8); moreover, membrane-bound antigens exist in association with other protein and lipid components of the membrane, so that sometimes these bystander molecules can be cocaptured with the cognate antigen (9). We speculated that if such bystander antigens were processed and presented to T cells, it would circumvent the antigen specificity of T-cell help.…”

Vaccine Adjuvant MF59 Promotes Retention of Unprocessed Antigen in Lymph Node Macrophage Compartments and Follicular Dendritic Cells

“…Follicular dendritic cells (FDCs) have been described to play a key role in the induction of B cell responses, particularly during reexposure of the immune system to a protein Ag (3)(4)(5)(6). FDCs capture circulating immune complexes (ICs) through the CR2 (CD21/35) and retain them for a long period (up to 3 wk) (3,5,(7)(8)(9). A prolonged exposure of the ICs on the FDC surface facilitates the encounter of the unprocessed Ag with cognate memory B cells (9,10).…”

“…FDCs capture circulating immune complexes (ICs) through the CR2 (CD21/35) and retain them for a long period (up to 3 wk) (3,5,(7)(8)(9). A prolonged exposure of the ICs on the FDC surface facilitates the encounter of the unprocessed Ag with cognate memory B cells (9,10). Moreover, FDCs secrete chemokines, such as CXCL13, to attract and interact with cognate B cells (5,6,9).…”

“…A prolonged exposure of the ICs on the FDC surface facilitates the encounter of the unprocessed Ag with cognate memory B cells (9,10). Moreover, FDCs secrete chemokines, such as CXCL13, to attract and interact with cognate B cells (5,6,9). Through this interaction, FDCs provide Ag-specific B cells with signals from the cognate Ag and the costimulatory surface or soluble molecules, which have to be integrated to achieve the selective activation of the memory B cells (4)(5)(6)(8)(9)(10)(11).…”

“…Moreover, FDCs secrete chemokines, such as CXCL13, to attract and interact with cognate B cells (5,6,9). Through this interaction, FDCs provide Ag-specific B cells with signals from the cognate Ag and the costimulatory surface or soluble molecules, which have to be integrated to achieve the selective activation of the memory B cells (4)(5)(6)(8)(9)(10)(11). FDCs maintain intact and unprocessed ICs, internalizing and recirculating them on the surface through a nondegradative vesicle trafficking pathway (12).…”