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Author Notes:

Correspondence: Sean R. Stowell srstowe@emory.edu

SP, DG, JH, and SS designed the research study.

SP carried out and analyzed experiments together with DG, KG-P, XZ, LR, RJ, MF, AB, and NS.

CM, CA, PZ, SC, CT, and JH provided critical support.

SP and SS wrote the manuscript, which was additionally edited and commented on by the others.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subject:

Research Funding:

his work was supported in part by the Burroughs Wellcome Trust Career Award for Medical Scientists, the National Institutes of Health (NIH) Early Independence grant DP5OD019892, R01HL135575, and P01HL132819 to SS. This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • marginal zone (MZ) B cells
  • RBC alloimmunization
  • follicular B cells
  • CD4 T cells
  • splenic marginal zone
  • RED-BLOOD-CELLS
  • MURINE MODEL
  • T-CELLS
  • ANTIGEN MODULATION
  • YOUNG-CHILDREN
  • FACTOR-VIII
  • PRECURSOR FREQUENCY
  • RESPONSE MAGNITUDE
  • IGM MEMORY
  • ALLOIMMUNIZATION

Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion

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Journal Title:

Frontiers in Immunology

Volume:

Volume 9, Number NOV

Publisher:

, Pages 2516-2516

Type of Work:

Article | Final Publisher PDF

Abstract:

Red blood cell (RBC) alloimmunization represents a significant immunological challenge for some patients. While a variety of immune constituents likely contribute to the initiation and orchestration of alloantibodies to RBC antigens, identification of key immune factors that initiate alloantibody formation may aid in the development of a therapeutic modality to minimize or prevent this process. To define the immune factors that may be important in driving alloimmunization to an RBC antigen, we determined the specific immune compartment and distinct cells that may initially engage transfused RBCs and facilitate subsequent alloimmunization. Our findings demonstrate that the splenic compartment is essential for formation of anti-KEL antibodies following KEL RBC transfusion. Within the spleen, transfused KEL RBCs are found within the marginal sinus, where they appear to specifically co-localize with marginal zone (MZ) B cells. Consistent with this, removal of MZ B cells completely prevented alloantibody formation following KEL RBC transfusion. While MZ B cells can mediate a variety of key downstream immune pathways, depletion of follicular B cells or CD4 T cells failed to similarly impact the anti-KEL antibody response, suggesting that MZ B cells may play a key role in the development of anti-KEL IgM and IgG following KEL RBC transfusion. These findings highlight a key contributor to KEL RBC-induced antibody formation, wherein MZ B cells facilitate antibody formation following RBC transfusion.

Copyright information:

© 2007 - 2018 Frontiers Media S.A.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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