A PROMISING MODEL OF PRIMARY HUMAN IMMUNIZATION IN HUMAN-SCID MOUSE

The engraftment of human peripheral blood mononuclear cells (Hu-PBMC) from adult donors in scid mice has been published by MOSIER ct al. in 1988. The possibility to obtain a secondary human immune response in h uman-scid mice has also been reported but attempts to induce a primary human immune response still remain difficult to achieve. In this work , an antigen (Canine albumin) or a hapten (DNP) was coupled with tetan us toroid, an antigenic protein against which our human donors already had memory T cells through vaccination. In this way, hu-scid mice imm unized with coupled DNP-tetanus toroid (TT-DNP) or coupled Canine albu min-Tetanus toroid (Calb-TT) mounted a specific human immune response anti-DNP or anti-Canine albumin (Calb) respectively. A secondary human immune response anti-tetanus toroid was also detected in the sera of hu-scid mice immunized with product containing TT but nor in the sera of those injected with PBS alone. The scid mice grafted with Hu-PBMC f rom a TT naive donor and challenged with Calb-TT or Calb alone failed to produce specific anti-Calb antibodies. These observations demonstra te that memory T cells can give a substantial help to naive B cells wh ich interact with them for obvious B cell activation and differentiati on into plasma cells. This model of immunization might be useful for o ther antigens of choice, allowing the production of human monoclonal a ntibodies, in combination with a suitable system of immortalization. A ttempts to immunize human cells in scid mice against DNP coupled to LO -BM2 (a rat monoclonal antibody anti-human IgM) failed to induce a spe cific human response either anti-rat immunoglobulins (Igs), or anti-DN P and led to a decrease of human Ig production in hu-scid. We also imm unized hu-scid mice against ovalbumin alone but, only in some cases, a low specific human immune response was observed, so this system seems to be unreliable.