A human monoclonal antibody to a human self-antigen, CD2 derived from human peripheral blood lymphocytes engrafted in SCID mice.
To establish human hybridoma lines, production of human immunoglobulin (Ig) and behavior of the implanted human peripheral blood lymphocytes (PBL) were characterized in severe combined immunodeficiency (SCID) mice. Human PBL from healthy donors were injected into the peritoneal cavity of SCID mice, and they were immunized with self-antigen, CD2. CD45+ cells (human PBL) migrated to lymphoid tissues in the mice as early as 4 days, accounting for more than half the lymph node cells and thymocytes. The number of cells releasing human IgG specific to the antigen increased 3.5 weeks after immunization without the usual constraint that production of the IgG, an autoantibody, is prohibited by immunological tolerance in humans. Therefore, we established several human hybridomas secreting human IgG to CD2, since splenocytes and lymph node cells from the implanted SCID mice at 3.5 weeks were fused with a human B lymphoblastoid cell line. A human anti-CD2 monoclonal antibody (MAb) was confirmed to bind to natural CD2 on human T cells by flow cytometric analysis. The epitope for the MAb was identical with a portion that the ligand LFA-3 binded, so that the MAb might reduce the inflammatory reaction caused by preventing activation of human T cells. Here, we report that the human immune system could be reconstituted in SCID mice to develop human hybridomas producing human MAb to a human self-antigen.
Discovery Research Laboratories II, Takeda Chemical Industries, LTD., Osaka, Japan.
N
N
Uchibayashi
R
R
Sasada
A
A
Shino
M
M
Okada
Y
Y
Ohkubo
T
T
Ochi
O
O
Shiho
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D018801:CD2 Antigens / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017634:Self Tolerance; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D007074:Immunoglobulin G