Evidence for restricted diversity of antigen-specific human antibodies in immunized hu-PBL-SCID mice.
Previous studies have revealed that specific human humoral immune responses could be produced in immunized SCID mice after engraftment of human lymphocytes (hu-PBL-SCID). On the other hand, the engrafted repertoire of B cell clones is known to be skewed in hu-PBL-SCID with the corresponding production of only a limited set of major human antibodies. In this work, we have analyzed the diversity of tetanus toxoid-specific human antibodies produced in immunized hu-PBL-SCID mice in comparison with the total serum antibody population using zone electrophoresis followed by blotting. The results showed that the diversity of tetanus toxoid-specific antibody population was more restricted than that of the total human antibody population, with some animal sera containing a single band of tetanus toxoid-specific antibody molecule, in clear contrast to the polyclonal response of the PBL donor. Absorption experiments showed tetanus toxoid-specific antibodies could account for a significant proportion (up to 10%) of the total human antibodies present in hu-PBL-SCID mouse sera. The inability to expand a high number of different antigen-specific B cell clones in immunized hu-PBL-SCID mice represents an important intrinsic limitation of this animal model which may be caused by defects in T cell help.
Bazin
R
R
Canadian Red Cross Society, Blood Services, Transfusion Centre of Québec, Canada.
Chevrier
M C
MC
Delage
R
R
Lemieux
R
R
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D016513:Mice, SCID
D000906:Antibodies; D007136:Immunoglobulins