Lymph nodes (LN) which are the sentinels of the immune system, are the site where lymphocytes engage cognate antigen and become activated. How antigen localizes to the lymph node and is “seen” by B and T cells is still not entirely clear; although it is apparent that follicular dendritic cells (FDC) are essential for retention of B cell antigens in germinal centers. Recently, we identified a novel mechanism whereby FDC take-up complement opsonized immune complexes (IC) via the CD21 receptor and cycle the complexes in a non-degradative endosomal compartment (Heesters et al 2013 Immunity). Early studies identified Human Immunodeficiency Virus (HIV) viral particles associated with FDC in the B cell follicles; where they are bound via complement receptor 2 (CD21) and/or Fc Receptors; but are not thought to become productively infected. Whether FDC act as a reservoir for infectious virus has been debated in the literature for over two decades. We propose that FDC retain infectious HIV virus similar to that identified for complement opsonized IC. Despite the success of antiretroviral therapy (ART), it does not cure HIV as discontinuation of treatment results in viral rebound. We found that human FDC isolated from LNs of patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4+ T cells in vitro. Importantly, treatment of the HIV+ FDC with soluble complement receptor 2 Ig fusion protein (sCD21-Ig) purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to limit this potential viral reservoir in HIV+ individuals.
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