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.
Lanemo Myhrinder
Anna
A
Department of Clinical and Experimental Medicine, Linköping University, Sweden.
Hellqvist
Eva
E
Sidorova
Ekaterina
E
Söderberg
Anita
A
Baxendale
Helen
H
Dahle
Charlotte
C
Willander
Kerstin
K
Tobin
Gerard
G
Bäckman
Eva
E
Söderberg
Ola
O
Rosenquist
Richard
R
Hörkkö
Sohvi
S
Rosén
Anders
A
D020816:Amino Acid Motifs / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D022801:Complementarity Determining Regions / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D019169:Jurkat Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D013058:Mass Spectrometry; D040081:Protein Array Analysis; D013296:Streptococcus pneumoniae / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D018956:CD5 Antigens; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein