Means and methods for influencing the stability of antibody producing cells
The invention provides a method for influencing the stability of an antibody producing cell, comprising directly or indirectly influencing the amount of BCL6 and/or Blimp 1 expression product within said antibody producing cell. Stable antibody producing cells and cell lines are also provided, as well as methods for producing antibodies using such cells and/or cell lines.
1. An antibody producing B cell that is capable of replicating for at least nine weeks, comprising:
an exogenous nucleic acid sequence encoding a peptide comprising Bcl6, or a functional part thereof, capable of increasing the replicative life span of an antibody producing B cell, and
an exogenous anti-apoptotic nucleic acid sequence; wherein the exogenous anti-apoptotic nucleic acid sequence encodes a member of the anti-apoptotic Bcl 2 family.
2. The antibody producing B cell according to claim 1 , wherein the exogenous anti-apoptotic nucleic acid sequence encodes a peptide comprising Bcl-xL, or a functional part thereof capable of increasing the replicative life span of an antibody producing B cell.
3. The antibody producing B cell according to claim 1 , wherein expression of the nucleic acid sequence encoding a peptide comprising Bc16, or a functional part thereof, is regulated by at least one of an activator and/or a repressor that is inducible by an exogenous compound.
4. A B cell culture, comprising antibody producing B cells according to claim 1 .
5. The B cell culture according to claim 4 , wherein the culture further comprises at least one of IL 21 and/or Il 10.
6. The antibody producing B cell according to claim 2 , wherein expression of the nucleic acid sequence encoding a peptide comprising Bcl6, Bcl-xL or a functional part of Bc16 or Bcl-xL, is regulated by at least one of an activator and/or a repressor that is inducible by an exogenous compound.