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Malaria infection alters the expression of B ‐cell activating factor resulting in diminished memory antibody responses and survival
Author(s) -
Liu Xue Q.,
Stacey Katryn J.,
HorneDebets Joshua M.,
Cridland Jasmyn A.,
Fischer Katja,
Narum David,
Mackay Fabienne,
Pierce Susan K.,
Wykes Michelle N.
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242689
Subject(s) - b cell activating factor , biology , malaria , plasmodium yoelii , antibody , immunology , immunity , b cell , immune system , virology , plasmodium falciparum , parasitemia
Malaria is a major cause of morbidity worldwide with reports of over 200–500 million infected individuals and nearly 1 million deaths each year. Antibodies have been shown to play a critical role in controlling the blood stage of this disease; however, in malaria‐endemic areas antibody immunity is slow to develop despite years of exposure to Plasmodium spp. the causative parasite. Using rodent P lasmodium yoelii YM , we provide evidence that malarial infections result in a decrease in the proportion of DC s that express the B ‐cell survival factor, BAFF , resulting in a decreased ability of these DC s to support memory B ‐cell differentiation into antibody secreting cells ( ASC s) and/or the survival of ASCs . Further, compared with infected WT mice, ASC numbers were significantly increased in malaria‐infected transgenic mice that either overexpressed BAFF or mice with BAFF ‐independent B ‐cell survival ( B ‐cell‐restricted TRAF 3 deletion). Remarkably, BAFF ‐overexpressing mice were protected from lethal malaria infections, indicating the significance of the role BAFF plays in determining the outcome of malaria infections. These findings describe a previously unappreciated mechanism by which P lasmodium spp. can depress the generation of protective antibody responses.