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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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NEOPLASIA
A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies
Anna Lanemo Myhrinder1,
Eva Hellqvist1,
Ekaterina Sidorova1,
Anita Söderberg1,
Helen Baxendale2,
Charlotte Dahle1,
Kerstin Willander1,
Gerard Tobin3,
Eva Bäckman1,
Ola Söderberg3,
Richard Rosenquist3,
Sohvi Hörkkö4, and
Anders Rosén1
1 Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;
2 Infectious Disease & Microbiology Unit, Institute of Child Health, University of London Medical School, London, United Kingdom;
3 Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden; and
4 Department of Pharmacology and Toxicology and Biocenter Oulu, University of Oulu, and Clinical Research Center, Oulu University Hospital, Oulu, Finland
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 has, however, not been characterized, although examples of autoantigens have been demonstrated. We have analyzed a panel of 28 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 (eg, Streptococcus pneumoniae polysaccharides and oxidized low-density lipoprotein [oxLDL]). 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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