Ann Lab Med 2020; 40(1): 48-56  https://doi.org/10.3343/alm.2020.40.1.48
Human B1 Cells are the Main Blood Group A-Specific B Cells That Have a Moderate Correlation With Anti-A Antibody Titer
Yixuan Xu, M.D.1,2, Jae-Ghi Lee, Ph.D.2, Ji-Jing Yan, M.D., Ph.D.2, Jung-Hwa Ryu, M.D., Ph.D.3, Songji Xu, M.D., Ph.D.1, and Jaeseok Yang, M.D., Ph.D.3,4
1Department of Preventive Medicine, Yanbian University College of Medicine, Yanji, Jilin, People’s Republic of China; 2Biomedical Research Institute, 3Transplantation Center, and 4Department of Surgery, Seoul National University Hospital, Seoul, Korea
Corresponding author: Jaeseok Yang, M.D., Ph.D.
Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-4128, Fax: +82-2-2072-4129, E-mail: jcyjs@snu.ac.kr

Songji Xu, M.D., Ph.D.
Department of Preventive Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin, People’s Republic of China
Tel: +86-433-2435271 Fax: +86-433-2435271 E-mail: yrge@ybu.edu.cn
Received: March 27, 2019; Revised: June 6, 2019; Accepted: July 31, 2019; Published online: January 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Anti-carbohydrate antibody responses, including those of anti-blood group ABO antibodies, are yet to be thoroughly studied in humans. Because anti-ABO antibody-mediated rejection is a key hurdle in ABO-incompatible transplantation, it is important to understand the cellular mechanism of anti-ABO responses. We aimed to identify the main human B cell subsets that produce anti-ABO antibodies by analyzing the correlation between B cell subsets and anti-ABO antibody titers.
Methods: Blood group A-binding B cells were analyzed in peritoneal fluid and peripheral blood samples from 43 patients undergoing peritoneal dialysis and 18 healthy volunteers with blood group B or O. The correlation between each blood group A-specific B cell subset and anti-A antibody titer was then analyzed using Pearson’s correlation analysis.
Results: Blood group A-binding B cells were enriched in CD27+CD43+CD1c B1, CD5+ B1, CD11b+ B1, and CD27+CD43+CD1c+ marginal zone-B1 cells in peripheral blood. Blood group A-specific B1 cells (P=0.029 and R=0.356 for IgM; P=0.049 and R=0.325 for IgG) and marginal zone-B1 cells (P=0.011 and R=0.410 for IgM) were positively correlated with anti-A antibody titer. Further analysis of peritoneal B cells confirmed B1 cell enrichment in the peritoneal cavity but showed no difference in blood group A-specific B1 cell enrichment between the peritoneal cavity and peripheral blood.
Conclusions: Human B1 cells are the key blood group A-specific B cells that have a moderate correlation with anti-A antibody titer and therefore constitute a potential therapeutic target for successful ABO-incompatible transplantation.
Keywords: Anti-ABO antibodies, Blood group A antigen, Human B1 cells, Human marginal zone B cells, Peritoneal B cells



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