Prion pathogenesis is unaltered following the transient depletion of marginal zone B cells

Aims:
Marginal zone B cells (MZB) function as a first-line of defence against blood-borne pathogens entering the spleen. MZB cells can mount rapid and efficient antibody responses to blood-borne antigens and can also transport immune complexes to, and deposit them on the surfaces of follicular dendritic cells. After infection via peripheral routes of exposure the early replication of prions upon FDC is important for their efficient spread to the brain. Since FDC are considered to initially acquire prions in the form of immune complexes, MZB cells have been implicated in early prion pathogenesis and may play a role in the initial delivery of prion agent to FDC. Our aim was to determine whether splenic MZB cells contribute to the early delivery of blood-borne prions from the splenic marginal zone to FDC in order to establish host infection.

Methods:
MZB cells were transiently depleted from the spleen by treating mice with -specific antibodies against the integrins CD11a and CD49d (integrin alpha L (LFA1) and V (VLA-4), respectively). This treatment blocks the binding and correct localisation of MZB cells in the spleen but does not affect other B-cell populations such as the follicular B cells. Following the transient depletion of MZB cells from the spleen (or control antibody treatment), mice were infected intravenously with ME7 scrapie prions. The effects of transient MZB cells depletion on prion disease pathogenesis and susceptibility were then determined.

Results:
Transient depletion of MZB cells via selective blockade of the integrins LFA1/VLA-4 had no observable effect on the expression of complement receptors and cellular PrPC by splenic FDC. Transient MZB depletion prior to intravenous prion infection also had no effect on the early accumulation of prions upon FDC within the spleen and their subsequent spread to the CNS. Mice depleted of MZB cells succumbed to clinical prion disease with similar survival times as control-treated mice. The prion-induced neuropathological changes in the brains of MZB cells depleted mice were also indistinguishable from control antibody treated mice.

Conclusions:
These data show that the lymphoid sequestration of intravenously administered prions to splenic FDC occurs just as efficiently in the presence or absence of MZB cells. These data therefore suggest that MZB cells are not required for the efficient delivery of blood-borne prions to FDC in order to establish host infection.