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

• 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.

Nyckelord

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

MEDICINE

MEDICIN

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