Generation of stable monoclonal antibody-producing BCR+ human memory B cells by genetic programming

By M. Kwakkenbos, S. Diehl, E. Yasuda, A. Bakker, Caroline M. M. van Geelen, M. Lukens, G. V. van Bleek, M. Widjojoatmodjo, W. Bogers, Henrik E. Mei and 4 more. 2009

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The B cell lymphoma-6 (Bcl-6) and Bcl-xL proteins are expressed in germinal center B cells and enable them to endure the proliferative and mutagenic environment of the germinal center. By introducing these genes into peripheral blood memory B cells and culturing these cells with two factors produced by follicular helper T cells, CD40 ligand (CD40L) and interleukin-21 (IL-21), we convert them to highly proliferating, cell surface B cell receptor (BCR)–positive, immunoglobulin-secreting B cells with features of germinal center B cells, including expression of activation-induced cytidine deaminase (AID). We generated cloned lines of B cells specific for respiratory syncytial virus and used these cells as a source of antibodies that effectively neutralized this virus in vivo. This method provides a new tool to study B cell biology and signal transduction through antigen-specific B cell receptors and for the rapid generation of high-affinity human monoclonal antibodies.

Subfields: Epidemiology, Immunology