Human B1 cells are the main blood group A-specific B cells that have a moderate correlation with anti-a antibody titer

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.