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 et al. in 1988. The possibility to obtain a secondary human immune response in human-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 tetanus toxoid, an antigenic protein against which our human donors already had memory T cells through vaccination. In this way, hu-scid mice immunized with coupled DNP-tetanus toxoid (TT-DNP) or coupled Canine albumin-Tetanus toxoid (Calb-TT) mounted a specific human immune response anti-DNP or anti-Canine albumin (Calb) respectively. A secondary human immune response anti-tetanus toxoid was also detected in the sera of hu-scid mice immunized with product containing TT but not in the sera of those injected with PBS alone. The scid mice grafted with Hu-PBMC from a TT naive donor and challenged with Calb-TT or Calb alone failed to produce specific anti-Calb antibodies. These observations demonstrate that memory T cells can give a substantial help to naive B cells which interact with them for obvious B cell activation and differentiation into plasma cells. This model of immunization might be useful for other antigens of choice, allowing the production of human monoclonal antibodies, in combination with a suitable system of immortalization. Attempts to immunize human cells in scid mice against DNP coupled to LO-BM2 (a rat monoclonal antibody anti-human IgM) failed to induce a specific human response either anti-rat immunoglobulins (Igs), or anti-DNP and led to a decrease of human Ig production in hu-scid. We also immunized 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.