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

Mark J. Kwakkenbos; Sean A. Diehl; Etsuko Yasuda; Arjen Q. Bakker; Caroline M. M. van Geelen; Michaël V. Lukens; Grada M. van Bleek; Myra N. Widjojoatmodjo; Willy M. J. M. Bogers; Henrik Mei; Andreas Radbruch; Ferenc A. Scheeren; Hergen Spits; Tim Beaumont

doi:https://doi.org/10.1038/nm.2071

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

Mark J. Kwakkenbos, Sean A. Diehl, Etsuko Yasuda, Arjen Q. Bakker, Caroline M. M. van Geelen, Michaël V. Lukens, Grada M. van Bleek, Myra N. Widjojoatmodjo, Willy M. J. M. Bogers, Henrik Mei, Andreas Radbruch, Ferenc A. Scheeren, Hergen Spits, Tim Beaumont

Research output: Contribution to journal › Article › Academic › peer-review

233 Citations (Scopus)

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. (C) 2010 Nature America, Inc. All rights reserved

Original language	English
Pages (from-to)	123-U164
Journal	Nature medicine
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/nm.2071
Publication status	Published - 2010

Access to Document

https://doi.org/10.1038/nm.2071

Cite this

Kwakkenbos, M. J., Diehl, S. A., Yasuda, E., Bakker, A. Q., van Geelen, C. M. M., Lukens, M. V., van Bleek, G. M., Widjojoatmodjo, M. N., Bogers, W. M. J. M., Mei, H., Radbruch, A., Scheeren, F. A., Spits, H., & Beaumont, T. (2010). Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nature medicine, 16(1), 123-U164. https://doi.org/10.1038/nm.2071

@article{6674720aa3ba49f689bc975cce61123e,

title = "Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming",

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. (C) 2010 Nature America, Inc. All rights reserved",

author = "Kwakkenbos, {Mark J.} and Diehl, {Sean A.} and Etsuko Yasuda and Bakker, {Arjen Q.} and {van Geelen}, {Caroline M. M.} and Lukens, {Micha{\"e}l V.} and {van Bleek}, {Grada M.} and Widjojoatmodjo, {Myra N.} and Bogers, {Willy M. J. M.} and Henrik Mei and Andreas Radbruch and Scheeren, {Ferenc A.} and Hergen Spits and Tim Beaumont",

year = "2010",

doi = "https://doi.org/10.1038/nm.2071",

language = "English",

volume = "16",

pages = "123--U164",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "1",

}

Kwakkenbos, MJ, Diehl, SA, Yasuda, E, Bakker, AQ, van Geelen, CMM, Lukens, MV, van Bleek, GM, Widjojoatmodjo, MN, Bogers, WMJM, Mei, H, Radbruch, A, Scheeren, FA, Spits, H & Beaumont, T 2010, 'Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming', Nature medicine, vol. 16, no. 1, pp. 123-U164. https://doi.org/10.1038/nm.2071

TY - JOUR

T1 - Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming

AU - Kwakkenbos, Mark J.

AU - Diehl, Sean A.

AU - Yasuda, Etsuko

AU - Bakker, Arjen Q.

AU - van Geelen, Caroline M. M.

AU - Lukens, Michaël V.

AU - van Bleek, Grada M.

AU - Widjojoatmodjo, Myra N.

AU - Bogers, Willy M. J. M.

AU - Mei, Henrik

AU - Radbruch, Andreas

AU - Scheeren, Ferenc A.

AU - Spits, Hergen

AU - Beaumont, Tim

PY - 2010

Y1 - 2010

N2 - 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. (C) 2010 Nature America, Inc. All rights reserved

AB - 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. (C) 2010 Nature America, Inc. All rights reserved

U2 - https://doi.org/10.1038/nm.2071

DO - https://doi.org/10.1038/nm.2071

M3 - Article

C2 - 20023635

SN - 1078-8956

VL - 16

SP - 123-U164

JO - Nature medicine

JF - Nature medicine

IS - 1

ER -