TY - JOUR TI - Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies AU - Rivera-Correa, Juan AU - Mackroth, Maria Sophia AU - Jacobs, Thomas AU - Schulze zur Wiesch, Julian AU - Rolling, Thierry AU - Rodriguez, Ana A2 - Krzych, Urszula A2 - Rath, Satyajit VL - 8 PY - 2019 DA - 2019/11/12 SP - e48309 C1 - eLife 2019;8:e48309 DO - 10.7554/eLife.48309 UR - https://doi.org/10.7554/eLife.48309 AB - Anemia is a common complication of malaria that is characterized by the loss of infected and uninfected erythrocytes. In mouse malaria models, clearance of uninfected erythrocytes is promoted by autoimmune anti-phosphatidylserine (PS) antibodies produced by T-bet+B-cells, which bind to exposed PS in erythrocytes, but the mechanism in patients is still unclear. In Plasmodium falciparum patients with anemia, we show that atypical memory FcRL5+T-bet+ B-cells are expanded and associate both with higher levels of anti-PS antibodies in plasma and with the development of anemia in these patients. No association of anti-PS antibodies or anemia with other B-cell subsets and no association of other antibody specificities with FcRL5+T-bet+ B-cells is observed, revealing high specificity in this response. We also identify FcRL5+T-bet+ B-cells as producers of anti-PS antibodies in ex vivo cultures of naïve human peripheral blood mononuclear cells (PBMC) stimulated with P.-falciparum-infected erythrocyte lysates. These data define a crucial role for atypical memory B-cells and anti-PS autoantibodies in human malarial anemia. KW - anemia KW - malaria KW - autoimmunity KW - atypical memory B-cells KW - autoantibodies KW - anti-phosphatidylserine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -