Human Immunoglobulins Produced in hu-PBL-SCID Mice Are Polyclonal Early after Xenotransplantation

Xenotransplantation of human peripheral blood leukocytes (hu-PBL) to severe combined immune-deficient (SCID, hu-PBL-SCID) mice leads to human immunoglobulin (Ig) production in the animals. Here we used a sensitive high-resolution two-dimensional electrophoresis (2D-PAGE) technique to separate, and to analyze, Ig γ and light chains in sera from SCID mice given hu-PBL for less than 35 days. Human Igs in the model appeared polyclonal until 3 weeks after cell transfer. After this period, oligoclonal Igs progressively replaced this polyclonal background. The 2D-PAGE pattern evolution of human Igs was similar when hu-PBL originated from donors with or without previous contact with the Epstein–Barr virus. The broad diversity of human Igs, and therefore the large expressed B cell repertoire, in hu-PBL-SCID mice during a period that allows manipulation (such as immunization) of the human graft has evident implication for the use of this model in the generation of specific antibodies of desired specificity.