Progressive B Cell Apoptosis and Expression of Fas Ligand during Human Immunodeficiency Virus Type 1 Infection

Abstract

HIV-1 infection causes functional defects in T cells. It also leads to a progressive reduction in numbers of such cells and both CD4+ and CD8+ cells have been reported to undergo apoptosis in culture. A corresponding reduction in B cells has not been described, but these cells are also functionally altered, with reports of polyclonal activation and hyporesponsiveness to antigenic and mitogenic stimuli. Here we investigated B cells from HIV-1-seropositive individuals and found that these cells, which are not the target for virus infection, died of apoptosis on culturing. We could also confirm previous findings that CD4+ cells from HIV-1-infected individuals undergo apoptosis in culture. Apoptosis of both B cells and CD4+ cells correlated inversely with CD4 cell counts. B cells from HIV-1-infected individuals were found to express Fas ligand, and the expression of this protein correlated with the levels of apoptosis in the same cells. Non-B cells, on the other hand, expressed increased levels of Fas but low levels of Fas ligand. These results are in line with suggestions that the Fas/Fas ligand pathway may trigger the increased levels of apoptosis observed in cells from HIV-1-infected individuals.

HIV Type 1 Glycoprotein 120 Inhibits Human B Cell Chemotaxis to CXC Chemokine Ligand (CXCL) 12, CC Chemokine Ligand (CCL)20, and CCL21

“…It may therefore play a role in the gp120-mediated increase in CD95 expression and CD95-mediated apoptosis in B cells. An increase in susceptibility to CD95 apoptosis may be involved in the depletion of peripheral B cells reported by several groups in HIV-infected patients (3,9,10,57). The gp120-induced decrease in membrane CD62L expression was dependent on CD4, CXCR4 triggering, and on the activation of G␣ i , p38 MAPK, and its cleavage by MMP.…”

“…with strong polyclonal B cell activation, increasing the percentage of activated B cells in the periphery (1)(2)(3)(4)(5), and with strong, sustained follicular hyperplasia in secondary lymphoid organs during the asymptomatic phase of the disease (6 -8). The B cells of HIV-infected patients spontaneously secrete Ig but are unable to mount a T cell-dependent B cell response (1,9,10).…”

“…Triggering of the BCR, CD40 and the IL-4R modulates chemokine receptor expression and chemotaxis in B cells (24 -26). Chemokines can bind to various pertussis toxin (PTX) 3 -sensitive (G␣ i ) and PTX-insensitive (G␣ q and G␣ 15/16 ) G␣ proteins, but chemotaxis is only observed upon activation of G␣ i protein-coupled receptors (22). There is strong evidence that G␤␥, rather than G␣ i subunits initiate the chemotactic response (27).…”

DATELINE Aix-les-Bains

“…Several reports indicate that this loss is due to apoptotic cell death of the CD4 + T cells (Ameisen, 1995) and that HIV-induced CD95-L expression might be, at least in part, responsible for this apoptotic cell death . Thus, infected and sensitised cells may not only die via autonomous CD95/ CD95-L interaction but may also kill non-infected sensitised T cells activated during infection of the human host (Kameoka et al, 1997;Samuelsson et al, 1997;Westerndorp et al, 1995) (M. Gougeon). Since most viruses pursue a strategy of avoiding host cell death rather than inducing it, HIV induced CD95-L expression might also serve another purpose.…”

“…Whether or not AICD in B cells is CD95/CD95-L dependent is still controversial (Daniel et al, 1997;Samuelsson et al, 1997;Scott et al, 1996;Truman et al, 1997). Nevertheless, germinal center and memory B cells express high CD95 levels and are thus potential targets for activated CD95-L expressing T cells.…”