Method of producing an antibody

Abstract

The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD/Shi mouse, and further backcrossing an interleukin 2-receptor γ-chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

1 - 11 . (canceled) 
     
     
         12 . A method of producing a human antibody comprising:
 introducing human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, into a mouse produced by a method comprising backcrossing a mouse B with a mouse A, wherein said mouse A is a mouse obtained by backcrossing a Severe Combined Immunodeficiency (SCID) mouse with a non-obese diabetic (NOD) mouse; and wherein said mouse B is an interleukin 2-receptor γ chain gene knockout mouse, wherein said mouse produced by the method retains the human B-cells or both human B cells and T-cells;   immunizing said mouse with an antigen; and   collecting the human antibody produced from the mouse.   
     
     
         13 . A method of producing an antibody-producing cell line which produces a human antibody, comprising:
 introducing human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, into a mouse produced by a method comprising backcrossing a mouse B with a mouse A, wherein said mouse A is a mouse obtained by backcrossing a Severe Combined Immunodeficiency (SCID) mouse with a non-obese diabetic (NOD) mouse; and wherein said mouse B is an interleukin 2-receptor γ chain gene knockout mouse, wherein said mouse produced by the method retains the human B-cells or both human B cells and T-cells;   immunizing said mouse with an antigen;   collecting from the mouse a cell which produced the antibody against the antigen; and   establishing a cell line of the cell.   
     
     
         14 . The method of  claim 12 , wherein the human B-cells, or both human B cells and T-cells, or human stem cells which differentiate into human B-cells or both human B cells and T-cells, are introduced intravenously. 
     
     
         15 . The method of  claim 12 , wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells, are CD34+ cells. 
     
     
         16 . The method of  claim 13 , wherein the antibody-producing cell is collected from the spleen. 
     
     
         17 . The method of  claim 13 , wherein the antibody-producing cell is collected from a lymph node. 
     
     
         18 . The method of  claim 12 , wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells are cord blood cells. 
     
     
         19 . The method of  claim 13 , wherein the human stem cells which differentiate into human B-cells or both human B cells and T-cells are cord blood cells.