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Nat Med. 2010 Jan;16(1):123-8. doi: 10.1038/nm.2071. Epub 2009 Dec 20.

Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming.

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1
AIMM Therapeutics, Academic Medical Center, Amsterdam, The Netherlands.

Abstract

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.

PMID:
20023635
PMCID:
PMC2861345
DOI:
10.1038/nm.2071
[Indexed for MEDLINE]
Free PMC Article

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