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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3838-3848.
Prepublished online as a Blood First Edition Paper on January 25, 2008; DOI 10.1182/blood-2007-11-125450.
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Submitted November 27, 2007
Accepted January 19, 2008
A new perspective: molecular motifs on oxidized-LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies
Anna Lanemo Myhrinder, Eva Hellqvist, Ekaterina Sidorova, Anita Soderberg, Helen Baxendale, Charlotte Dahle, Kerstin Willander, Gerard Tobin, Eva Backman, Ola Soderberg, Richard Rosenquist, Sohvi Horkko, and Anders Rosen*
Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
Infectious Disease & Microbiology Unit, Institute of Child Health, University of London Medical School, London, United Kingdom
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
Department of Pharmacology and Toxicology and Biocenter Oulu, University of Oulu, and Clinical Research Center, Oulu University Hospital, Oulu, Finland
* Corresponding author; email: anders.rosen{at}ibk.liu.se.
The restricted immunoglobulin (Ig) repertoire found in B-cell chronic lymphocytic leukemia (CLL) implies a role for antigen(s) in the leukemogenesis. The nature of the antigens have, however, not been characterized, although examples of autoantigens have been demonstrated. We have analyzed a panel of twenty-eight CLL cell lines and primary cultures, producing monoclonal Ig with different Ig heavy-chain variable region gene usage and mutational status, including several complementarity determining region 3 homology subset members. Using mass-spectrometry, immunoassays, or protein-macroarrays, we have discovered novel antigens binding to CLL Igs. These antigens included cytoskeletal proteins vimentin, filamin B, and cofilin-1, but also phosphorylcholine-containing antigens e.g. Streptococcus pneumoniae polysaccharides and oxidized-LDL. Additional new antigens identified were cardiolipin and proline-rich acidic protein-1. Remarkably, these antigens represent molecular motifs exposed on apoptotic cells/blebs and bacteria; and several CLL Igs bound to apoptotic Jurkat cells. In conclusion, these intriguing data, showing a limited target structure recognition, indicate that CD5+ CLL B-cells are derived from a cell-compartment that produces 'natural antibodies', which may be instrumental in elimination and scavenging of apoptotic cells and pathogenic bacteria.
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