Characterization of Anti-Gal Antibody-Producing Cells of Baboons and Humans
| Autor: | Megan Sykes, Hideki Ohdan, Yong-Guang Yang, A. Thall, David Ryan, Michel Awwad, Huw S. Kruger-Grey, D. Harper, C Wu, Y. Xu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Syndecans
Spleen Disaccharides Antigen medicine Animals Humans Antibody-Producing Cells CD20 Transplantation Membrane Glycoproteins CD40 biology ELISPOT Antigens CD20 Flow Cytometry B-1 cell medicine.anatomical_structure Immunoglobulin M Immunoglobulin G Immunology Splenectomy biology.protein Proteoglycans Syndecan-1 Bone marrow Antibody Papio |
| Zdroj: | Transplantation. 81:940-948 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000203300.87272.a3 |
| Popis: | Background. Anti-Gal antibodies cause hyperacute and delayed xenograft rejection in pig-to-primate transplantation. The cell populations producing anti-Gal and other natural antibodies in primates are unknown. Methods. Cells from different lymphoid compartments of naive or sensitized baboons were examined for anti-Gal and total Ig production by ELISPOT. B and plasma cells from humans and baboons were purified by FACS sorting and characterized for anti-Gal and total Ig production and cytology. Results. In naive baboons, the spleen was the major source of anti-Gal IgM-secreting cells. Two months after sensitization with porcine tissues, high frequencies of anti-Gal IgM- and IgG-secreting cells were detected in the spleen, lymph nodes, and bone marrow. Six months after antigen exposure, anti-Gal IgM- and IgG-secreting cells were preferentially localized in the bone marrow. Cells from human spleen, bone marrow, and blood were also analyzed and anti-Gal IgM-secreting cells were detected mainly in the spleen. Sorting of baboon and human cells showed that anti-Gal IgM-secreting cells were mainly splenic B cells (CD20 + , CD138 - , and Ig + ). Although low in percentage, sorted CD20-CD138 + plasma cells in spleen and bone marrow secreted large quantities of anti-Gal IgM. Most anti-Gal IgG-secreting cells were plasma cells (CD138 + ) at both early (Ig + ) and late (Ig - ) stages of differentiation. Conclusions. Similar to Gal knockout mice, natural anti-Gal IgM antibodies in primates are produced mainly by splenic B cells. After antigen exposure, anti-Gal IgM and IgG were secreted by both B and plasma cells. These results suggest strategies to remove xenoreactive antibody-secreting cells prior to transplantation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|