Methods for generation of antibodies

Abstract

This invention generally relates to methods for the production of antibody producing cells and antibodies in protooncogene expressing animals. The invention also relates to methods for the efficient production of antibodies specific for antigens that are normally subject to immunological constraints such as self tolerance. The invention further relates to the production of antibody producing cells and antibodies without the need for the conventional fusing of antibody producing B cells with a myeloma fusion partner.

1 - 61 . (canceled) 
     
     
         62 . A method for preparing an antibody producing cell with antibody specificity for an antigen of interest, comprising: exposing the antigen of interest to a non-human animal that overexpresses MYC in an inducible manner, wherein the overexpression of MYC is regulated in a temporal manner, such that MYC is not overexpressed until the production of antibodies is desired, and wherein overexpression of MYC enables B cells to produce antibodies specific for the antigen of interest. 
     
     
         63 . The method of  claim 62 , wherein the non-human animal produces MYC as the result of genetic modification. 
     
     
         64 . The method of  claim 63 , wherein the inducible MYC is MYC-ER. 
     
     
         65 . The method of  claim 62 , wherein the non-human animal produces MYC as the result of natural or directed mutation. 
     
     
         66 . The method of any one of  claim 62 , wherein the non-human animals overexpress MYC predominantly in the B cell population. 
     
     
         67 . The method of any one of  claim 62 , wherein the non-human animal is exposed to an antigen by introduction of an exogenous antigen into the non-human animal. 
     
     
         68 . The method of any one of  claim 62 , wherein the non-human animal is exposed to the antigen by introduction of cells transduced with the antigen. 
     
     
         69 . The method of  claim 68 , wherein the cells transduced with the antigen are hematopoietic stem cells. 
     
     
         70 . The method of any one of  claim 62 , wherein the non-human animal is exposed to the antigen by engineering the non-human animal to express the antigen. 
     
     
         71 . The method of any one of  claim 62 , wherein the non-human animal is a rodent. 
     
     
         72 . The method of  claim 71 , wherein the rodent is a mouse. 
     
     
         73 . The method of  claim 62 , wherein the antigen comprises an antoantigen. 
     
     
         74 . The method of  claim 62 , wherein the antigen comprises an HIV protein or an antigen from an influenza virus. 
     
     
         75 . The method of  claim 62 , wherein the antibody is a human antibody. 
     
     
         76 . An antibody producing cell with antibody specificity for an antigen of interest, comprising: a B cell that overexpresses MYC in an inducible manner, wherein the B cell is engineered to express the antigen of interest, and wherein temporal overexpression of MYC enables the production of antibodies specific for the antigen of interest. 
     
     
         77 . The antibody producing cell of  claim 76 , wherein the cell inducibly overexpresses MYC as the result of genetic modification. 
     
     
         78 . The antibody producing cell of  claim 77 , wherein the inducible MYC is MYC-ER. 
     
     
         79 . A hematopoietic stem cell capable of giving rise to a population of B cells having antibodies specific for an antigen of interest, comprising: an inducible MYC that can be temporally overexpressed; and a transduced antigen of interest; wherein overexpression of MYC in the population of B cells enables the B cells to produce antibodies specific for the antigen of interest. 
     
     
         80 . The hematopoietic stem cell of  claim 79 , wherein the cell inducibly overexpresses MYC as the result of genetic modification. 
     
     
         81 . The hematopoietic stem cell of  claim 80 , wherein the inducible MYC is MYC-ER.