Means and methods for influencing the stability of cells
View Patent ↗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. A B cell culture comprising:
B cells comprising an exogenous nucleic acid sequence encoding BCL6 or a functional part thereof; and
a compound that is capable of enhancing Blimp-1 expression.
2. The B cell culture of claim 1 , wherein said compound capable of enhancing Blimp-1 expression comprises IL-21, IL-2, IL-6, IL-7, IL-10, IL-15, IL-27, a SOCS protein, a mutated Janus kinase and/or a nucleic acid sequence encoding STAT3 or a functional part, derivative and/or analogue thereof.
3. The B cell culture of claim 2 , comprising:
B cells comprising an exogenous nucleic acid sequence encoding BCL6 or a functional part thereof; and
IL-21 and/or IL-10.
4. A B cell culture comprising B cells, the cells comprising:
an exogenous nucleic acid sequence encoding BCL6 or a functional part thereof; and
an exogenous nucleic acid sequence encoding STAT3 or a functional part thereof capable of upregulating Blimp 1 expression.
5. The B cell culture of claim 1 , wherein the B cells comprise an exogenous nucleic acid sequence encoding constitutively active BCL6.
6. A B cell culture comprising:
B cells comprising an exogenous nucleic acid sequence encoding STAT5 or a functional part thereof capable of directly or indirectly enhancing BCL6 expression; and
IL-10 and/or IL-21.
7. The B cell culture of claim 5 , wherein the B cells comprise an exogenous nucleic acid sequence encoding constitutively active STAT5.
8. The B cell culture of claim 1 , wherein the B cells are antibody producing B cells.
9. The B cell culture of claim 1 , wherein the B cells produce an antibody of interest.
10. The B cell culture of claim 9 , wherein the antibody producing B cells have been obtained from an individual, which individual had been previously exposed to an antigen of interest.
11. An antibody producing cell comprising:
an exogenous nucleic acid sequence encoding BCL6 or a functional part thereof; and
IL-21 and/or IL-10.
12. An antibody producing cell comprising:
an exogenous nucleic acid sequence encoding BCL6 or a functional part thereof; and
an exogenous nucleic acid sequence encoding STAT3 or a functional part thereof capable of upregulating Blimp-1 expression.
13. The antibody producing cell of claim 11 , comprising an exogenous nucleic acid sequence encoding constitutively active BCL6.
14. An antibody producing cell that is stable for at least nine weeks, the cell comprising:
an exogenous nucleic acid sequence encoding STAT5 or a functional part thereof capable of directly or indirectly enhancing BCL6 expression; and
IL10 and/or IL-21.
15. The B cell culture of claim 4 , wherein the B cells comprise an exogenous nucleic acid sequence encoding constitutively active BCL6.
16. The B cell culture of claim 2 , wherein the B cells are antibody producing B cells.
17. The B cell culture of claim 6 , wherein the B cells are antibody producing B cells.
18. The B cell culture of claim 2 , wherein the B cells produce an antibody of interest.
19. The B cell culture of claim 6 , wherein the B cells produce an antibody of interest.
20. The antibody producing cell of claim 12 , comprising an exogenous nucleic acid sequence encoding constitutively active BCL6.