Journal article
Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation
The Journal of experimental medicine, Vol.218(6), e20202359
06/07/2021
DOI: 10.1084/jem.20202359
PMCID: PMC8040514
PMID: 33830176
Abstract
Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite-infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.
Details
- Title: Subtitle
- Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation
- Creators
- Rahul Vijay - University of IowaJenna J. Guthmiller - University of ChicagoAlexandria J. Sturtz - University of IowaSequoia Crooks - University of IowaJordan T. Johnson - University of IowaLei Li - University of ChicagoLinda Yu-Ling Lan - University of ChicagoRosemary L. Pope - University of ChicagoYani Chen - University of IowaKai J. Rogers - University of IowaNirmal Dutta - University of IowaJason E. Toombs - The University of Texas Southwestern Medical CenterMary E. Wilson - University of IowaPatrick C. Wilson - University of ChicagoWendy Maury - University of IowaRolf A. Brekken - The University of Texas Southwestern Medical CenterNoah S. Butler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.218(6), e20202359
- DOI
- 10.1084/jem.20202359
- PMID
- 33830176
- PMCID
- PMC8040514
- NLM abbreviation
- J Exp Med
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Publisher
- Rockefeller Univ Press
- Number of pages
- 16
- Grant note
- P30CA086862 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) S10OD016199 / National Center for Research Resources of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) I01BX001983; 2I01BX000536 / US Department of Veterans Affairs T32AI007511; R01AI134733; R21AI139902; P01AI097092; HHSN272201400005C; R01AI125446; R01AI127481 / National Institutes of Health/National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) T32HL007605 / National Institutes of Health/National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 06/07/2021
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984297331702771
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