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

Blood. 2008 Apr 1;111(7):3838-48. doi: 10.1182/blood-2007-11-125450. Epub 2008 Jan 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / immunology
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neoplasm / immunology*
  • Antibody Specificity / immunology
  • Antigens, Bacterial / immunology*
  • Antigens, Neoplasm / immunology*
  • Apoptosis / immunology*
  • CD5 Antigens / immunology
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Complementarity Determining Regions / immunology
  • Humans
  • Immunoglobulin Heavy Chains / immunology
  • Jurkat Cells
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lipoproteins, LDL / immunology*
  • Mass Spectrometry
  • Protein Array Analysis
  • Streptococcus pneumoniae / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, Bacterial
  • Antigens, Neoplasm
  • CD5 Antigens
  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Lipoproteins, LDL
  • oxidized low density lipoprotein