In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb)
| Autor: | D, Harper, B, Gollackner, Y, Xu, D, Calderhead, D, Ryan, W, Li, J, Cheng, C, Wu, K, Moran, D, Latinne, H, Bazin, M E, White-Scharf, D K C, Cooper, M, Awwad, J, Chang |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.drug_class
Plasma Cells Immunology Bone Marrow Cells Disaccharides Monoclonal antibody Antibodies Epitope Immunoglobulin G Epitopes In vivo medicine Animals Lymphocyte Count Cells Cultured B-Lymphocytes Transplantation biology ELISPOT Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Rats Inbred Strains HLA-DR Antigens Flow Cytometry Precipitin Tests Molecular biology Blood Cell Count Rats Phenotype medicine.anatomical_structure Immunoglobulin M biology.protein Female Immunization Lymph Nodes Bone marrow Antibody Spleen Papio |
| Zdroj: | Xenotransplantation. 11:78-90 |
| ISSN: | 1399-3089 0908-665X |
| Popis: | Natural antibodies (Abs), predominantly anti-Gal alpha 1-3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naïve baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments. |
| Databáze: | OpenAIRE |
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