Human B1 Cells are the Main Blood Group A-Specific B Cells That Have a Moderate Correlation With Anti-A Antibody Titer

Ann Lab Med. 2020 Jan;40(1):48-56. doi: 10.3343/alm.2020.40.1.48.

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.

MeSH terms

  • ABO Blood-Group System / immunology
  • Adult
  • Antibodies / blood*
  • Antigens, CD1 / metabolism
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / pathology
  • Leukosialin / metabolism
  • Male
  • Middle Aged
  • Peritoneal Dialysis
  • Prospective Studies

Substances

  • ABO Blood-Group System
  • Antibodies
  • Antigens, CD1
  • CD1C protein, human
  • Glycoproteins
  • Leukosialin