Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies

TY - JOUR

T1 - 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

N1 - © 2019, Rivera-Correa et al.

PY - 2019/11/12

Y1 - 2019/11/12

N2 - 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.

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.

U2 - 10.7554/eLife.48309

DO - 10.7554/eLife.48309

M3 - SCORING: Journal article

C2 - 31713516

VL - 8

JO - ELIFE

JF - ELIFE

SN - 2050-084X

ER -