Document 0187
 DOCN  M95A0187
 TI    Human/mouse radiation chimera are capable of mounting a human primary
       humoral response.
 DT    9510
 AU    Marcus H; David M; Canaan A; Kulova L; Lubin I; Segall H; Denes L;
       Erlich P; Galun E; Gan J; et al; Department of Membrane Research and
       Biophysics, Weizmann; Institute of Science, Rehovot, Israel.
 SO    Blood. 1995 Jul 1;86(1):398-406. Unique Identifier : AIDSLINE
       MED/95315565
 AB    Lubin et al recently described a new approach that enables the
       generation of human/mouse chimera by adoptive transfer of human
       peripheral blood mononuclear cells (PBMC) into lethally irradiated
       normal strains of mice, radioprotected with bone marrow (BM) from donors
       with severe combined immune deficiency (SCID). In the present study, we
       demonstrate in such human/mouse chimera a marked humoral response to
       recall antigen, such as tetanus toxoid (TT) or hepatitis B surface
       antigen (HBsAg), as well as a significant primary response to keyhole
       limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera
       was attained 2 to 4 weeks after the immunization and declined
       thereafter. One week after transplantation, the predominant anti-KLH
       subtype was IgM, while after 2 weeks, the dominance had shifted to IgG.
       Similar primary antibody response was also demonstrated against the
       human immunodeficiency virus (HIV) Nef protein. Comparison between
       human/Balb and human/SCID chimera showed a major difference in their
       ability to mount a primary response against KLH. In Balb/c recipients,
       more than half of the mice exhibited marked IgM titers against KLH,
       while there was hardly any anti-KLH IgM response in the SCID recipients.
       From the earliest time point onwards, when anti-KLH antibodies were
       found in the latter chimera, 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.
 DE    Animal  *Antibody Formation  Antibody Specificity  Bone Marrow
       Transplantation  Cell Movement  Hemocyanin/IMMUNOLOGY  Hepatitis B
       Surface Antigens/IMMUNOLOGY  Human  IgG/BIOSYNTHESIS/IMMUNOLOGY
       IgM/BIOSYNTHESIS/IMMUNOLOGY  *Immunologic Memory  *Immunotherapy,
       Adoptive  *Leukocyte Transfusion  Lymphocyte Depletion  Lymphoid
       Tissue/IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred C3H  Mice,
       SCID  Radiation Chimera/*IMMUNOLOGY  Support, Non-U.S. Gov't  Tetanus
       Toxoid/IMMUNOLOGY  Transplantation, Heterologous  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).