A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies
2008 (English)In: Blood, ISSN 0006-4971, Vol. 111, no 7, 3838-3848 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 111, no 7, 3838-3848 p.
Amino Acid Motifs/immunology, Antibodies; Monoclonal/*immunology, Antibodies; Neoplasm/*immunology, Antibody Specificity/immunology, Antigens; Bacterial/*immunology, Antigens; CD5/immunology, Antigens; Neoplasm/*immunology, Apoptosis/*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
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-16381DOI: 10.1182/blood-2007-11-125450ISI: 000254569300073PubMedID: 18223168OAI: oai:DiVA.org:uu-16381DiVA: diva2:44152