This supports suggestions that the role of B-cells in PML is multi-faceted, independent of antibody secretion and related to altered cell-mediated immunity; for example, B-cell-deficient IgM knockout mice lose their normal CD4 and CD8 response to a lymphocytic choriomeningitis virus (LCMV) variant, whilst non-IgM secretory B-cell-replete mice retained this function [19, 20]. Here, CD8A is linked to progressive multifocal leukoencephalopathy.