NOD/SCID mice engrafted with human peripheral blood lymphocytes can be a model for investigating B cells responding to blood group A carbohydrate determinant.
Human antibodies (Abs) against blood group A or B carbohydrate determinant are a major barrier to ABO-incompatible organ transplantation; however, the phenotype and other properties of B cell types responding to A or B carbohydrate epitopes have not been defined. Studies here, which use fluorescein-labeled synthetic A determinant (GalNAcalpha1-3Fucalpha1-2Gal), demonstrate that B cells bearing surface IgM (sIgM) receptors recognizing blood group A carbohydrate determinant are found exclusively in a small B cell subpopulation, i.e. sIgM+ CD11b+ CD5+ B1 cells, in blood group O human peripheral blood mononuclear cells (PBMC). In order to test anti-A Abs producing capacity of the human PBMC, nonobese diabetic (NOD)/severe combined immune-deficient (SCID) mice that have been treated with rabbit anti-asialo GM1 serum to deplete natural killer cells and with 3 Gy of whole body irradiation were engrafted with blood group O or A human PBMC, followed by sensitization of human blood group A red blood cells. Anti-A-specific human Abs were detected in the sera of the mice that received blood group O human PBMC, whereas they were not detected in the sera of the mice that received blood group A human PBMC, indicating profound tolerance of auto-reactive B cells. The human PBMC-NOD/SCID chimera developed by injection of blood group O human PBMC might be a useful in vivo model to test effects of immunosuppressants or other approaches on human B cells that respond to blood group A antigens.
Zhou
Wendy
W
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan.
Ohdan
Hideki
H
Tanaka
Yuka
Y
Hara
Hidetaka
H
Tokita
Daisuke
D
Onoe
Takashi
T
Asahara
Toshimasa
T
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000737:chemistry; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001789:Blood Group Antigens / Q000276:immunology; D001835:Body Weight / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000032:analysis / Q000097:blood; D007272:Injections, Intralymphatic; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D017708:Leukocyte Transfusion / Q000009:adverse effects; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D010529:Peritoneal Cavity / Q000166:cytology; D011961:Receptors, Fc / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
D000017:ABO Blood-Group System; D015703:Antigens, CD; D001789:Blood Group Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D011961:Receptors, Fc; C035311:immunoglobulin M receptor