In vitro germinal centers

A method for immortalizing B cells expressing antibodies having binding specificity for a selected antigen comprising:

• a) administering a selected antigen to an in vitro cellular system, wherein the in vitro cellular system comprises a culture comprising an engineered tissue construct, and at least one three-dimensional artificial germinal center embedded in or fixed on the engineered tissue construct, wherein the artificial germinal center comprises a plurality of follicular dendritic cells, a plurality of B cells, and a plurality of T cells;
• b) culturing the system of a) under conditions promoting activation of B cells expressing antibodies having binding specificity for the antigen;
• c) isolating B cells expressing antibodies having binding specificity for the antigen from the system of b);
• and
• d) immortalizing the B cells producing antibodies having binding specificity for the antigen.

A method for immortalizing B cells monoclonal for a selected antigen comprising:

• a) administering a selected antigen to an in vitro cellular system, wherein the in vitro cellular system comprises a culture comprising an engineered tissue construct, and at least one three-dimensional artificial germinal center embedded in or fixed on the engineered tissue construct, wherein the artificial germinal center comprises a plurality of follicular dendritic cells, a plurality of B cells, and a plurality of T cells;
• b) culturing the system of a) under conditions promoting activation of B cells monoclonal for the selected antigen;
• c) identifying B cells that are monoclonal for the antigen in the culture of b);
• and
• d) isolating, cloning and immortalizing the B cells monoclonal for the antigen, thereby immortalizing B cells monoclonal for a selected antigen.