ANTIGEN-SPECIFIC HUMORAL IMMUNE-RESPONSES TO A HAPTEN-CARRIER CONJUGATE IN SCID MICE ENGRAFTED WITH BOVINE FETAL HEMATOPOIETIC TISSUES

We describe the conditions necessary to reconstitute a bovine immune s ystem in SCID mice that supports the generation of antigen-specific se rum antibody responses to a hapten carrier (DNP-KLH) conjugate, Sublet hally irradiated SCID mice were engrafted with fetal bovine liver, lym ph node, and thymus, Treatment groups were established in which human recombinant interleukin 7, autologous bovine bone marrow, and engraftm ent site (omentum or abdominal wall) were evaluated for their ability to enhance the reconstitution of the bovine immune system in SCID mice , Engrafted SCID mice were inoculated at approximately 6 and 12 weeks after engraftment with DNP-KLH. Vaccinated mice were evaluated by enzy me-linked immunosorbent assay for serum antibody specific for DNP-KLH and total concentrations of bovine serum immunoglobulin biweekly throu gh 20 weeks after engraftment, The SCID mice with fetal tissues engraf ted onto the abdominal wall from two different donors produced microgr am quantities of bovine immunoglobulins and had >70% reconstitution ra te, Administration of human interleukin 7 and/or fetal bovine bone mar row did not significantly increase the frequency of reconstitution, Su bclass analysis of serum from mice receiving the abdominal implants su ggested that class-switching occurred to a predominant non-IgM isotype response after the second inoculation, Pooled thymic and splenic cell populations obtained 20 weeks after engraftment from abdominally engr afted groups yielded 38 to 90% bovine cells, as determined by polymera se chain reaction in situ hybridization with bovine satellite DNA-spec ific primers, These results indicate that an antigen-specific bovine i mmune response can be generated in heterochimeric SCLD-bo mice.