HUMAN-IMMUNOGLOBULINS PRODUCED IN HU-PBL-SCID MICE ARE POLYCLONAL EARLY AFTER XENOTRANSPLANTATION

Xenotransplantation of human peripheral blood leukocytes (hu-PBL) to s evere combined immune-deficient (SCID, hu-PBL-SCID) mice leads to huma n immunoglobulin (Ig) production in the animals, Here we used a sensit ive high-resolution two-dimensional electrophoresis (2D-PAGE) techniqu e to separate, and to analyze, Ig gamma and light chains in sera from SCID mice given hu-PBL for less than 35 days. Human Igs in the model a ppeared polyclonal until 3 weeks after cell transfer. After this perio d, oligoclonal Igs progressively replaced this polyclonal background. The 2D-PAGE pattern evolution of human Igs was similar when hu-PBL ori ginated 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 evid ent implication for the use of this model in the generation of specifi c antibodies of desired specificity. (C) 1996 Academic Press, Inc.