Characterization of anti-Gal antibody-producing cells of baboons and humans.
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.
Xu
Yuanxin
Y
Immerge BioTherapeutics, Cambridge, MA, USA.
Yang
Yong-Guang
YG
Ohdan
Hideki
H
Ryan
David
D
Harper
David
D
Wu
Cecelia
C
Kruger-Grey
Huw S
HS
Thall
Aron D
AD
Awwad
Michel
M
Sykes
Megan
M
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D018951:Antigens, CD20 / Q000032:analysis; D004187:Disaccharides / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008562:Membrane Glycoproteins / Q000032:analysis; D010215:Papio; D011509:Proteoglycans / Q000032:analysis; D013156:Splenectomy; D053668:Syndecan-1; D053667:Syndecans
D018951:Antigens, CD20; D004187:Disaccharides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; C055075:galactosyl-(1-3)galactose