Characterization of anti-Gal antibody-producing cells of baboons and humans

Yuanxin Xu, Yong Guang Yang, Hideki Ohdan, David Ryan, David Harper, Cecelia Wu, Huw S. Kruger-Grey, Aron D. Thall, Michel Awwad, Megan Sykes

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 naïve 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 naïve 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.

Original languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalTransplantation
Volume81
Issue number6
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Anti-Gal
  • Antibody-secreting cells
  • B cells
  • Plasma cells

ASJC Scopus subject areas

  • Transplantation

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    Xu, Y., Yang, Y. G., Ohdan, H., Ryan, D., Harper, D., Wu, C., Kruger-Grey, H. S., Thall, A. D., Awwad, M., & Sykes, M. (2006). Characterization of anti-Gal antibody-producing cells of baboons and humans. Transplantation, 81(6), 940-948. https://doi.org/10.1097/01.tp.0000203300.87272.a3