A new perspective: molecular motifs on oxidized-LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies

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Blood First Edition Paper, prepublished online January 25, 2008; DOI

10.1182/blood-2007-11-125450.

A new perspective: molecular motifs on oxidized-LDL, apoptotic cells, and

bacteria are targets for chronic lymphocytic leukemia antibodies

Lanemo Myhrinder, Eva Hellqvist, Ekaterina Sidorova, Anita Soderberg, Helen

Baxendale, Charlotte Dahle, Kerstin Willander, Gerard Tobin, Eva Backman, Ola

Soderberg, 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@... .

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.