Suppression of allo-human leucocyte antigen ( HLA) antibodies secreted by B memory cells in vitro: intravenous immunoglobulin ( IVIg) versus a monoclonal anti- HLA- E IgG that mimics HLA- I reactivities of IVIg.

IMMUNOSUPPRESSION; LEUCOCYTES; ANTIGENS; B cells; IN vitro studies; MONOCLONAL antibodies; IMMUNOGLOBULIN G

B memory cells remain in circulation and secrete alloantibodies without antigen exposure > 20 years after alloimmunization postpartum or by transplantation. These long-lived B cells are resistant to cytostatic drugs. Therapeutically, intravenous immunoglobulin ( IVIg) is administered to reduce allo-human leucocyte antigen ( HLA) antibodies pre- and post-transplantation, but the mechanism of reduction remains unclear. Recently, we reported that IVIg reacts with several HLA- I alleles and the HLA reactivity of IVIg is lost after its HLA- E reactivity is adsorbed out. Therefore, we have generated an anti- HLA- E monoclonal antibody that mimics the HLA-reactivity of IVIg to investigate whether this antibody suppresses IgG secretion, as does IVIg. B cells were purified from the blood of a woman in whose blood the B memory cells remained without antigen exposure > 20 years after postpartum alloimmunization. The B cells were stimulated with cytokines using a well-defined culture system. The anti- HLA- E monoclonal antibody (m Ab) significantly suppressed the allo- HLA class- II IgG produced by the B cells, and that this suppression was far superior to that by IVIg. These findings were confirmed with HLA- I antibody secreted by the immortalized B cell line, developed from the blood of another alloimmunized woman. The binding affinity of the anti- HLA- E m Ab for peptide sequences shared (i.e. shared epitopes) between HLA- E and other β2-microglobulin-free HLA heavy chains (open conformers) on the cell surface of B cells may act as a ligand and signal suppression of IgG production of activated B memory cells. We propose that anti- HLA- E monoclonal antibody may also be useful to suppress allo- HLA IgG production in vivo. [ABSTRACT FROM AUTHOR]