Memory B cells are required to maintain long-lived plasma cells in mice following viral infections (132.16)

Abstract

Abstract Antibody responses have been found to last for life following lymphocytic choriomeningitis virus (LCMV) infection in mice and have been estimated to have a half-life of up to 200 years for some pathogens in humans. These antibodies are produced by long-lived plasma cells which have been shown to have a half-life of at least 138 days in mice. However, the role of memory B cells in the maintenance of plasma cell numbers remains unclear. We have been attempting to define this role by infecting hCD20 transgenic mice with viral pathogens, treating them with rituximab (an anti-CD20 antibody), and then following the antibody levels in these mice. Rituximab treatment of hCD20 mice selectively depletes naive and memory B cells while leaving plasma cells untouched. During long-term treatment of LCMV immune mice, there is a slow, steady decline of antibody levels and a decrease in the number of LCMV-specific antibody secreting cells in the spleen and bone marrow. This decrease in antibody levels was also observed with influenza and vesicular stomatitis virus (VSV) infected mice and correlates with decreased hemagglutination inhibition titers in influenza infections and decreased neutralization titers in VSV infections. These results suggest a critical role for memory B cells in the maintenance of long-lived plasma cells following viral infections. This work was supported by NIH grant AI30048.