Identification of a polyclonal B-cell activator in Plasmodium falciparum.
Polyclonal B-cell activation and hypergammaglobulinemia are prominent features of human malaria. We report here that Plasmodium falciparum-infected erythrocytes directly adhere to and activate peripheral blood B cells from nonimmune donors. The infected erythrocytes employ the cysteine-rich interdomain region 1alpha (CIDR1alpha) of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to interact with the B cells. Stimulation with recombinant CIDR1alpha induces proliferation, an increase in B-cell size, expression of activation molecules, and secretion of immunoglobulins (immunoglobulin M) and cytokines (tumor necrosis factor alpha and interleukin-6). Furthermore, CIDR1alpha binds to Fab and Fc fragments of human immunoglobulins and to immunoglobulins purified from the sera of different animal species. This binding pattern is similar to that of the polyclonal B-cell activator Staphylococcus aureus protein A. Our findings shed light on the understanding of the molecular basis of polyclonal B-cell activation during malaria infections. The results suggest that the var gene family encoding PfEMP1 has evolved not only to mediate the sequestration of infected erythrocytes but also to manipulate the immune system to enhance the survival of the parasite.
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Daria
D
Donati
Li Ping
LP
Zhang
Arnaud
A
Chêne
Qijun
Q
Chen
Kirsten
K
Flick
Maja
M
Nyström
Mats
M
Wahlgren
Maria Teresa
MT
Bejarano
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism*
D007136:Immunoglobulins; D015800:Protozoan Proteins; D000511:alpha-Macroglobulins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C032306:polyclonal B cell activator