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 system in SCID mice that supports the generation of antigen-specific serum antibody responses to a hapten-carrier (DNP-KLH) conjugate. Sublethally irradiated SCID mice were engrafted with fetal bovine liver, lymph node, and thymus. Treatment groups were established in which human recombinant interleukin 7, autologous bovine bone marrow, and engraftment 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 enzyme-linked immunosorbent assay for serum antibody specific for DNP-KLH and total concentrations of bovine serum immunoglobulin biweekly through 20 weeks after engraftment. The SCID mice with fetal tissues engrafted onto the abdominal wall from two different donors produced microgram quantities of bovine immunoglobulins and had >70% reconstitution rate. Administration of human interleukin 7 and/or fetal bovine bone marrow did not significantly increase the frequency of reconstitution. Subclass analysis of serum from mice receiving the abdominal implants suggested 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 engrafted groups yielded 38 to 90% bovine cells, as determined by polymerase chain reaction in situ hybridization with bovine satellite DNA-specific primers. These results indicate that an antigen-specific bovine immune response can be generated in heterochimeric SCID-bo mice.