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 culture, comprising:
at least one of IL-21 and/or IL-10; and
B cells, said B cells comprising an exogenous nucleic acid sequence, said 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.
2. The antibody producing B cell culture according to claim 1 , wherein the B cells further comprise an exogenous anti-apoptotic nucleic acid sequence.
3. The antibody producing B cell culture according to claim 2 , wherein the exogenous anti-apoptotic nucleic acid sequence encodes a member of the anti-apoptotic Bcl 2 family.
4. The antibody producing B cell culture according to claim 2 , 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.
5. The antibody producing B cell culture according to claim 4 , wherein expression of the nucleic acid sequence encoding Bcl6 or Bcl-xL, or a functional part of Bcl6 or Bcl-xL, is regulated by at least one of an activator and/or repressor that is inducible by an exogenous compound.
6. The antibody producing B cell culture according to claim 1 , wherein the B cells further comprise an exogenous compound capable of directly or indirectly enhancing Bcl xL expression.
7. The antibody producing B cell culture according to claim 6 , wherein the compound comprises at least one of APRIL, BAFF, CD40, BCR stimulation, cytokines, growth factors or downstream effector(s).
8. The antibody producing B cell culture according to claim 1 , wherein the B cells are capable of replicating for at least nine weeks.
9. The antibody producing B cell culture according to claim 1 , wherein the B cells are capable of producing antibodies against an antigen of interest.
10. The antibody producing B cell culture according to claim 9 , wherein the B cells are derived from an individual, which individual had been previously exposed to said antigen of interest.