LIMITATIONS OF THE SEVERE COMBINED IMMUNODEFICIENCY (SCID) MOUSE MODEL FOR STUDY OF HUMAN B-CELL RESPONSES

Mice lacking functional T and B lymphocytes offer an in who animal mod el for the study of human immune functions. We have attempted to optim ize the reconstitution of severe combined immunodeficiency (SCID) mice with human peripheral blood lymphocytes (PBL) using radiation, anti-a sialo GM(1) antibody or cyclophosphamide (Cy) treatment of the mice an d in vitro stimulation of human PBL with interleukin (IL)-2 prior to t heir transfer to the mice. Total human IgG and tetanus-toroid (TT)-spe cific human IgG responses of the mice were used as parameters of succe ssful reconstitution. Treatment of the mice with anti-asialo GM(1) ant ibody significantly enhanced total human IgG levels, but not TT-specif ic antibody responses, whereas irradiation or Cy treatment of the mice had no effect on human antibody production. In vitro treatment of hum an PBL with IL-2 prior to engraftment significantly decreased total hu man IgG responses of human PBL-grafted SCID mice. The immune responses of individual mice within a group were highly variable, which constit utes a major disadvantage of this model.