Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies.
Human PBL from vaccinated healthy blood donors, which was transplanted i.p. into mice with severe combined immunodeficiency (SCID), exhibited an Ag-dependent humoral Ir against tetanus toxoid. This Ir was dose dependent and was completely abrogated by immunizing with large amounts of Ag, suggesting a high dose tolerization of the B cells. A dose-dependent selection of specific, high affinity B clonotypes was also suggested, since immunization with low concentrations of tetanus toxoid produced antisera with higher avidity than immunizations using a high dose of Ag. The production of human Ig and the clonal outgrowth of normal human B cells in the SCID mouse was strongly down-regulated by human NK cells. Human immune B lymphocytes were also recovered from immunized SCID mice and transformed with EBV, yielding lymphoblastoid cell lines producing high affinity antitetanus human IgG antibodies. These results suggest that SCID mice, repopulated with human PBL, can constitute a functional model of several parameters of a normal human humoral Ir and can provide a source of immune B cells for the production of human mAb.
Carlsson
R
R
BioInvent International AB, Lund, Sweden.
Mårtensson
C
C
Kalliomäki
S
S
Ohlin
M
M
Borrebaeck
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000911:Antibodies, Monoclonal; D013745:Tetanus Toxoid