Malaria infection alters the expression of B‐cell activating factor resulting in diminished memory antibody responses and survival

• Published in: European journal of immunology Vol. 42; no. 12; pp. 3291 - 3301
• Main Authors: Liu, Xue Q., Stacey, Katryn J., Horne‐Debets, Joshua M., Cridland, Jasmyn A., Fischer, Katja, Narum, David, Mackay, Fabienne, Pierce, Susan K., Wykes, Michelle N.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.12.2012
• Subjects: Animals; Antibodies, Protozoan - genetics; Antibodies, Protozoan - immunology; Antibodies, Protozoan - metabolism; Antibody Formation - genetics; B-Cell Activating Factor - biosynthesis; B-Cell Activating Factor - genetics; B-Cell Activating Factor - immunology; BAFF; Cell Differentiation - immunology; Cell Survival - genetics; Cell Survival - immunology; DCs; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Humans; Immunologic Memory; Infections; Malaria; Malaria - genetics; Malaria - immunology; Malaria - metabolism; Memory B cells; Mice; Mice, Transgenic; Plasma Cells - immunology; Plasma Cells - metabolism; Plasmodium; Plasmodium yoelii - immunology; Rodents
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242689

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 Plasmodium yoelii YM, we provide evidence that malarial infections result in a decrease in the proportion of DCs that express the B‐cell survival factor, BAFF, resulting in a decreased ability of these DCs to support memory B‐cell differentiation into antibody secreting cells (ASCs) 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 TRAF3 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 Plasmodium spp. can depress the generation of protective antibody responses.