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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.
NEOPLASIA A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies1 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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