Offspring of xenogeneically-reconstituted scid/scid mice are capable of a primary xenogeneic immune response to DNP-KLH

Human peripheral blood leukocyte (PBL) reconstitution of severe combined immunodeficient (SCID) mice has provided a small animal model system (hu-PBL-SCID) useful for the study of the human immune system and disease pathogenesis. Transfer of xenogeneic PBL from donors other than humans has also been successful; however, the controversy remains regarding the capability of xenogeneically engrafted lymphocytes to mount a primary immune response. Human cells have been identified in offspring from hu-PBL-SCID but were not evaluated for a primary immune response. In the present study, offspring of bovine PBL-reconstituted SCID mice (F1-PBL-SCID-bo) were assessed for specific immune function. Sera from all of the F1-PBL-SCID-bo contained relatively low levels of bovine IgG 5 weeks after birth but bovine Ig became undetectable by 14 or 18 weeks. Eight F1-PBL-SCID-bo (23 or 27 weeks of age) were immunized with a single dose of 100 μg dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH). Individual cells secreting bovine antibody were enumerated using the ELISA-plaque assay. One week after immunization, bovine cells secreting bovine immunoglobulin (IgG) specific for DNP-KLH were identified in the spleens from three of the F1-PBL-SCID-bo at a frequency of one antibody-secreting cell per 9 × 103 to 1 × 106 spleen cells. Thus, xenogeneic lymphocytes, passed from the mother to her offspring, retain the capacity for a primary immune response to DNP-KLH.