Anti-CD5 monoclonal antibody, clone 2I7/9 [FITC]

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.

The innate B cell (IBC) population is heterogeneous and involved in the primary immune response. IBC functions include a high ability to produce natural antibodies with IgM isotype, the elimination of apoptotic cells, and a capacity to be cognate help to T cells. Among IBC subsets, B-1 cells and marginal zone B cells are the main producers of IgM, act as rapid immune responders that may relocate to follicular lymphoid and differentiate to cytokine and antibody-secreting cells shortly after infection. IBCs functions are highly dependent on their localization site and the nature of their B cell receptor repertoire, suggesting a high plasticity range of different immune responses. In this review, we will describe the nature and functions of the different innate-like B cell subsets, first in mice and then in humans. Besides this, we will emphasize the strong ability of these cells to undertake different protective functions from the first line of defense against pathogens to the regulatory role of the broader immune response.