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*
Innogenetics N.V., Ghent-Zwijnaarde, Belgium; and
Center for Vaccinology and
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University and Hospital, Ghent, Belgium
Human mAbs (HumAbs) have therapeutic potential against infectious
diseases and cancer. Heretofore, their production has been hampered by
ethical constraints preventing the isolation of Ag-specific activated B
cells by in vivo immunization. Alternatively, severe combined immune
deficient (SCID) mice, transplanted i.p. with human (Hu)-PBLs, allow
the in vivo stimulation of human Ab responses without the usual
constraints. Unfortunately, human B cells only represent a minor
fraction of the surviving graft, they are scattered all over the animal
body, and thus are hard to isolate for subsequent immortalization
procedures. To prevent this dispersion and to provide the human B cells
with a niche for expansion and maturation, SCID mice were engrafted
with Hu-PBL directly into the spleen. Simultaneously endogenous murine
NK cell activity was depleted by treatment with an anti-mouse IL-2
receptor 
-chain Ab. During engraftment, human B lymphocytes became
activated, divided intensely, and differentiated into plasmacytoid
cells. In vivo exposure to a recall Ag after cell transfer induced
expansion of Ag-specific B cell clones. One week after inoculation,
human B cells were abundant in the spleen and could easily be recovered
for fusion with a heteromyeloma line. This resulted in the formation of
stable hybridoma cell lines that secreted Ag-specific HumAbs. Thus
transplantation of human lymphoid cells in the spleens of immune
deficient mice represents a model for the study of human T
cell-dependent B cell activation and proves to be an excellent tool for
the successful production of HumAbs.
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