BAFF and BAFF Receptor Levels Correlate with B Cell Subset Activation and Redistribution in Controlled Human Malaria Infection

作者：Scholzen Anja; Teirlinck Anne C; Bijker Else M; Roestenberg Meta; Hermsen Cornelus C; Hoffman Stephen L; Sauerwein Robert W^*

来源：The Journal of Immunology, 2014, 192(8): 3719-3729.

DOI：10.4049/jimmunol.1302960

Characteristic features of Plasmodium falciparum malaria are polyclonal B cell activation and an altered composition of the blood B cell compartment, including expansion of CD21(-)CD27(-) atypical memory B cells. BAFF is a key cytokine in B cell homeostasis, but its potential contribution to the modulation of the blood B cell pool during malaria remains elusive. In the controlled human malaria model (CHMI) in malaria-naive Dutch volunteers, we therefore examined the dynamics of BAFF induction and B cell subset activation and composition, to investigate whether these changes are linked to malaria-induced immune activation and, in particular, induction of BAFF. Alterations in B cell composition after CHMI closely resembled those observed in endemic areas. We further found distinct kinetics of proliferation for individual B cell subsets across all developmental stages. Proliferation peaked either immediately after blood-stage infection or at convalescence, and for most subsets was directly associated with the peak parasitemia. Concomitantly, plasma BAFF levels during CHMI were increased and correlated with membrane-expressed BAFF on monocytes and dendritic cells, as well as blood-stage parasitemia and parasite-induced IFN-gamma. Correlating with increased plasma BAFF and IFN-gamma levels, IgD(-)CD38(low)CD21(-)CD27(-) atypical B cells showed the strongest proliferative response of all memory B cell subsets. This provides unique evidence for a link between malaria-induced immune activation and temporary expansion of this B cell subset. Finally, baseline BAFF-R levels before CHMI were predictive of subsequent changes in proportions of individual B cell subsets. These findings suggest an important role of BAFF in facilitating B cell subset proliferation and redistribution as a consequence of malaria-induced immune activation.

• 出版日期2014-4-15