Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses

Sullivan, Meghan; Kaur, Kaval; Pauli, Noel; Wilson, Patrick C.

Even with advances to increase the efficiency of transformation, these methods still suffer from several drawbacks. First, viral transformation causes cells lines to be unstable. Second, memory B cells were used to produce the cell lines. Since memory B cells represent the entire immunological history of the patient and not necessarily the infection or vaccination of interest, it is not guaranteed that all or most of these monoclonal antibodies will be relevant. This makes it necessary to screen many cell lines before a relevant clone is identified. Third, as this method relies on the transformation of cells from the memory compartment in particular, transient cells that arise during infection, such as plasmablasts, are overlooked. This prevents researchers from discerning between antibodies that arise during a current immune response and those that previously arose during historic immune responses and merely cross-react to the current antigen. This is an important consideration for pathogens such as influenza, which rapidly mutate due to selective pressure. Therefore, antibodies elicited by one variant will be less effective in clearing another, allowing the latter virus to escape antibodies from past immune responses.