Composition comprising B regulatory cells

1. An isolated population of cells, wherein the population comprises human Breg cells, having the phenotype CD19 + CD73 − CD71 + CD25 + TIM-1 + , and wherein the human Breg cells additionally have the phenotype CD154 + .

2. The isolated cell population of claim 1 , wherein at least 50% of the human Breg cells in the cell population express CD19 and at least 50% of the human Breg cells in the cell population do not express CD73 and at least 50% of the human Breg cells in the cell population express CD71 and at least 50% of the human Breg cells in the cell population express CD25 and at least 50% of the human Breg cells in the cell population express TIM-1.

3. The isolated cell population of claim 1 , wherein the human Breg cells additionally have a phenotype selected from the group consisting of IL-10R + and CD39 + .

4. The isolated cell population of claim 1 , wherein the human Breg cells additionally have a phenotype selected from the group consisting of CD5 − , CD1d − , CD24 − , CD27 − , CD21 − and CD38 − .

5. The isolated cell population of claim 1 , wherein less than 30% of the human Breg cells in the cell population express IL-10.

6. The isolated cell population of claim 1 , wherein at least 50% of the cells in the population are human Breg cells having the phenotype CD19 + CD73 − CD71 + CD25 + TIM-1 + or CD19 + CD73 − CD71 + CD25TIM-1 + CD154 + .

7. A pharmaceutical composition comprising the isolated population of cells according to claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 wherein the isolated population of cells comprises at least 50% of the composition.

9. A method for producing a human Breg cell population comprising:

isolating human CD19 + B cells;

culturing said CD19 + B cells in the presence of CD154, or peptide fragments thereof, and/or cells expressing CD154, and at least one cytokine or growth factor for at least 3 days;

harvesting the Breg cells so produced.

10. The method according to claim 9 , wherein culturing said CD19 + B cells in the presence of a CD40 agonist comprises culturing the CD19 + B cells in the presence of cells expressing CD154 and wherein the cells expressing CD154 and the CD19 + B cells are cultured at a ratio of 1:1.

11. The method according to claim 9 , wherein the at least one cytokine is selected from the group consisting of IL-2, IL-4 and IL-10, and combinations thereof.

12. The method according to claim 9 , wherein the at least one cytokine comprises IL-21; or (ii) wherein IL-21 is not added during culturing of the human CD19 + B cells.

13. The method according to claim 9 , wherein the human CD19 + B cells are cultured for between 3-60 days, optionally 3-7 days.

14. The method of claim 9 , wherein the human Breg cells are expanded by at least 200 fold.

15. The method according to claim 9 , wherein the human CD19 + B cells are isolated from a patient sample.

16. The method according to claim 9 , wherein the human CD19 + B cells are isolated from a patient sample, and wherein the patient sample is a blood sample.

17. The method according to claim 9 , wherein the Breg cells produced have the phenotype CD19 + CD73 − CD71 + CD25 + TIM-1 + or CD19 + CD73 − CD71 + CD25 + TIM-1 + CD154 + .

18. The method according to claim 9 , wherein the harvested cells comprise at least 80% human Breg cells.

19. An expanded human Breg cell population obtained by

isolating human CD19 + B cells,

culturing said CD19 + B cells in the presence of cells expressing CD154 at a ratio of 1:1, and at least one cytokine or growth factor for at least 3 days, and

harvesting the Breg cells so produced.

20. The method according to claim 9 further comprising genetically modifying said human CD19 + B cells prior to expansion, to express a target antigen, wherein the target antigen is associated with an immune-mediated disorder.