HUMAN MOUSE RADIATION CHIMERA ARE CAPABLE OF MOUNTING A HUMAN PRIMARYHUMORAL RESPONSE

Lubin et al recently described a new approach that enables the generat ion of human/mouse chimera by adoptive transfer of human peripheral bl ood mononuclear cells (PBMC) into lethally irradiated normal strains o f mice, radioprotected with bone marrow (BM) from donors with severe c ombined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antig ens, such as tetanus toroid (TT) or hepatitis B surface antigen (HBsAS ), as well as a significant primary response to keyhole limpet hemocya nin (KLH). Maximal anti-KLH response in human/Balb chimera was attaine d 2 to 4 weeks after the immunization and declined thereafter. One wee k after transplantation, the predominant anti-KLH subtype was IgM, whi le after 2 weeks, the dominance had shifted to IgG. Similar primary an tibody response was also demonstrated against the human immunodeficien cy virus (HIV) Nef protein. Comparison between human/Balb and human/SC ID chimera showed a major difference in their ability to mount a prima ry response against KLH. In Balb/c recipients, more than half of the m ice exhibited marked IgM titers against KLH, while there was hardly an y anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chim era, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells. (C) 1995 by The American Soci ety of Hematology.