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Human immunoglobulins produced in hu-PBL-SCID mice are polyclonal early after xenotransplantation
J D Tissot1, P Schneider, M Schapira
1Fondation Centre de transfusion sanguine CRS, Lausanne, Switzerland.
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 gamma 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.
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 gamma 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.