Molecular characterization of neoplastic and normal “sister” lymphoblastoid B-cell lines from chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.

Keywords::

• Chronic lymphocytic leukemia (CLL)
• lymphoblastoid cell line (LCL)
• IGHV sequence
• cell-of-origin
• natural antibodies
• antigen structure
• CD5 + innate B-cells

Acknowledgements

We would like to acknowledge the authors of the original reports for their contributions and for sharing the cell lines with us or making them available via depositions to cell banks.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This study was funded by the Swedish East Gothia Cancer Foundation, Linköping University Hospital Funds. M.H. received support relevant to these studies from the Deutsche Forschungsgemeinschaft (HE3553/2-1), a Deutsche Krebshilfe Max-Eder program, the CLLGRF, and the BMBF (Federal Ministry of Education and Research, Germany; grant number 01 KI 0771). K.N., E.K., R.R. and A.R. were funded by the Swedish Cancer Society, and R.R. and A.R. by the Swedish Research Council, GSD.