CD19(+) B cells confer protection against experimental cerebral malaria in semi-immune rodent model

• Published in: PloS one 2013-05, Vol.8 (5), p.e64836-e64836
• Main Authors: Bao, Lam Quoc, Huy, Nguyen Tien, Kikuchi, Mihoko, Yanagi, Tetsuo, Senba, Masachika, Shuaibu, Mohammed Nasir, Honma, Kiri, Yui, Katsuyuki, Hirayama, Kenji
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Adults; Animals; Antibodies, Protozoan - blood; Antigens, CD19 - metabolism; B-Lymphocytes - immunology; Biology; CD19 antigen; CD5 antigen; CD5 Antigens - metabolism; Children; Disease Models, Animal; Disease Resistance - immunology; Disease Susceptibility; Extracellular matrix; Immune status; Immunity; Immunoglobulin G - blood; Immunology; Infections; Interferon; Interferon-gamma - blood; Interleukin 10; Interleukin-10 - biosynthesis; Interleukin-10 - blood; Lymphocytes; Lymphocytes B; Malaria; Malaria, Cerebral - blood; Malaria, Cerebral - immunology; Malaria, Cerebral - parasitology; Malaria, Cerebral - prevention & control; Mathematics; Medicine; Mice; Mice, Inbred C57BL; Mortality; Parasitemia - immunology; Parasitemia - parasitology; Parasites; Pathogenesis; Plasmodium berghei; Plasmodium berghei - physiology; Species Specificity; Spleen; Spleen - pathology; Vector-borne diseases; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064836

In African endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. Here, we developed an experimental cerebral malaria (ECM) model for semi-immune mice. C57BL/6 (B6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 10(4) Plasmodium berghei ANKA without treatment. Our results showed that 100% of naïve (0-cure), 67% of 1-cure, 37% of 2-cure and none of 3-cure mice succumbed to ECM within 10 days post challenge infection. In the protected 3-cure mice, significantly higher levels of plasma IL-10 and lower levels of IFN-γ than the others on day 7 post challenge infection were observed. Major increased lymphocyte subset of IL-10 positive cells in 3-cure mice was CD5(-)CD19(+) B cells. Passive transfer of splenic CD19(+) cells from 3-cure mice protected naïve mice from ECM. Additionally, aged 3-cure mice were also protected from ECM 12 and 20 months after the last challenge infection. In conclusion, mice became completely resistant to ECM after three exposures to malaria. CD19(+) B cells are determinants in protective mechanism of semi-immune mice against ECM possibly via modulatory IL-10 for pathogenic IFN-γ production.