Exogenous 4-1BB Co-Stimulation Enhances Memory B Cell Response During Malaria

Clearance of the malarial parasite and protection from reinfection is dependent on T helper cell-dependent germinal center (GC) -derived plasma cells (PC) and memory B cells (MBC). Enhancing or blocking T cell help during experimental malaria has been shown to either improve or impede GC output, respectively. Using a mouse model of malaria, we show that an agonistic antibody against the co-stimulatory molecule, 4-1BB (CD137), hinders an optimal GC response, but enhances humoral immune memory. We demonstrate that this apparent paradox is at least partially driven by CD4 T cell-intrinsic Eomesodermin expression. By using chemoprophylaxis or irradiated parasites we show that the beneficial effects of 4-1BB ligation on humoral immune memory are neither influenced by the inflammatory milieu, nor due to an increased number of MBCs, but rather due to their heightened recall capacity and their ability to readily differentiate into antibody secreting PCs.### Competing Interest StatementThe authors have declared no competing interest.