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In vitro induction of antibody secretion of primary B-cell chronic lymphocytic leukaemia cells

Leukemia volume 29, pages 244–247 (2015)Cite this article

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We and others have shown that antigen-dependent B-cell receptor signalling plays a pivotal role in the development of B-cell chronic lymphocytic leukaemia (CLL). The immunoglobulin (Ig) heavy-chain variable region (IGHV) gene repertoire used by CLLs is biased to frequent usage of IGHV1-69, IGHV3-7 and IGHV4-34,1 and over 30% of CLLs can be grouped in over 100 stereotypic subsets based on similarities of the amino-acid sequences in the highly variable complementary determining region 3,2, 3, 4, 5 strongly suggesting that distinctive antigens are involved in their development. In support, we have recently elucidated the antigenic specificity of two stereotypic mutated CLL subsets. One subset was found to express high-affinity IgM for the Fc-tail of the self-antigen IgG, so called rheumatoid factors,6 and a second mutated CLL subset expressed IGHV3-7 that are highly specific for the fungal cell wall component beta-(1,6)-glucan.7

We identified cognate antigens recognized by membrane-expressed CLL Igs by recombinant production in the SP2/0 myeloma cell line, which is a laborious and time-consuming method.6,7 Other investigators generated recombinant CLL-derived antibodies (Abs) in non-B-cell lineage cell lines, which may yield Abs that are differently glycosylated as compared to those produced by B-lineage cell lines or primary CLL cells in vivo. In addition, CLL Abs have been produced as F(ab) fragments, which may have different avidity and affinity. To overcome these disadvantages and expedite the identification of CLL antigen specificities, we explored methods to obtain secreted Abs from in vitro cultured CLL cells. Previous attempts to produce soluble Abs by in vitro stimulation of CLL cells have been hampered by rapid spontaneous apoptosis8 and/or yielded only minute amounts of Abs.9, 10, 11

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Acknowledgements

This work was financially supported by the Dutch Cancer Society, grant UVA 2006-3644.

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Authors and Affiliations

  1. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    R Hoogeboom, R J A Reinten, J E J Guikema, R J Bende & C J M van Noesel

  2. Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    J-J Schot

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  1. R Hoogeboom
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Correspondence to C J M van Noesel.

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Hoogeboom, R., Reinten, R., Schot, JJ. et al. In vitro induction of antibody secretion of primary B-cell chronic lymphocytic leukaemia cells. Leukemia 29, 244–247 (2015). https://doi.org/10.1038/leu.2014.266

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