FDCs are located in hot spots of immune activity in lymphoid tissue called germinal centers. They act like flypaper, trapping invading pathogens (including HIV) and holding them until B cells come along to initiate an immune response.

Close on the heels of B cells are CD4+ T cells, which rush into the germinal centers to help B cells fight the invaders. CD4+ T cells, the primary targets of HIV, may become infected as they encounter HIV trapped on FDCs. Research suggests that HIV trapped on FDCs remains infectious, even when coated with antibodies. Thus, FDCs are an important reservoir of HIV, and the large quantity of infectious HIV trapped on FDCs may explain in part how the momentum of HIV infection is maintained Once infected, CD4+ T cells may infect other CD4+ cells that congregate in the region of the lymph node surrounding the germinal center.

Over a period of years, even when little virus is readily detectable in the blood, significant amounts of virus accumulate in the lymophoid tissue, both within infected cells and bound to FDCs. In and around the germinal centers, numerous CD4+ T cells are probably activated by the increased production of cytokines such as TNF-alpha and IL-6 by immune system cells within the lymphoid tissue. Activation allows uninfected cells to be more easily infected and increases replication of HIV in already infected cells.

While greater quantities of certain cytokines such as TNF-alpha and IL-6 are secreted during HIV infection, other cytokines with key roles in the regulation of normal immune function may be secreted in decreased amounts. For example, CD4+ T cells may lose their capacity to produce interleukin 2 (IL-2), a cytokine that enhances the growth of other T cells and helps to stimulate other cells' response to invaders. Infected cells also have low levels of receptors for IL-2, which may reduce their ability to respond to signals from other cells.



Breakdown of FDC networks

Ultimately, accumulated HIV overwhelms the FDC networks. As these networks break down, their trapping capacity is impaired, and large quantities of virus enter the bloodstream.

Although it remains unclear why FDCs die and the FDC networks dissolve, some scientists think that this process may be as important in HIV pathogenesis as the loss of CD4+ T cells. The destruction of the lymphoid tissue structure seen late in HIV disease may preclude a successful immune response against not only HIV but other pathogens as well. This devastation heralds the onset of the opportunistic infections and cancers that characterize AIDS.

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