title: 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.
abstract: 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.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA, USA; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.forename: M H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: V
authors.initials: V
authors.lastname: Jucaud
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D059806:HLA-DR beta-Chains / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007518:Isoantibodies / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D055815:Young Adult; D000097625:HLA-E Antigens
chemical_list: D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D006680:HLA Antigens; D059806:HLA-DR beta-Chains; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D000097625:HLA-E Antigens
keywords: B memory cells; HLA-reactivity; allo-HLA IgG; immunosuppression; intravenous immunoglobulin (IVIg)