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

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 (mAb) 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 mAb 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.