title: BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection.
abstract: 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-γ. Correlating with increased plasma BAFF and IFN-γ 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.
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
authors.forename: Anne C
authors.initials: AC
authors.lastname: Teirlinck
authors.forename: Else M
authors.initials: EM
authors.lastname: Bijker
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000097:blood / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008288:Malaria / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology / Q000469:parasitology; D018512:Parasitemia / Q000097:blood / Q000276:immunology / Q000469:parasitology; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C423544:FCRL4 protein, human; D011961:Receptors, Fc