Chronic lymphocytic leukemia cells recognize conserved epitopes associated with apoptosis and oxidation.

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Chronic lymphocytic leukemia cells recognize conserved epitopes associated with

apoptosis and oxidation.

R Catera, GJ Silverman, K Hatzi, T Seiler, S Didier, L Zhang, M Herve, E Meffre,

DG Oscier, H Vlassara, RH Scofield, Y Chen, SL , J Kolitz, KR Rai, CC Chu,

and N Chiorazzi

Mol Med, November 1, 2008; 14(11-12): 665-74.

Feinstein Institute for Medical Research, North Shore-LIJ Health System,

Manhasset, New York 11030, USA.

Chronic lymphocytic leukemia (CLL) represents the outgrowth of a CD5(+) B cell.

Its etiology is unknown. The structure of membrane Ig on CLL cells of unrelated

patients can be remarkably similar. Therefore, antigen binding and stimulation

could contribute to clonal selection and expansion as well as disease promotion.

Initial studies suggest that CLL mAbs bind autoantigens. Since apoptosis can

make autoantigens accessible for recognition by antibodies, and also create

neo-epitopes by chemical modifications occurring naturally during this process,

we sought to determine if CLL mAbs recognize autoantigens associated with

apoptosis. In general, ~60% of CLL mAbs bound the surfaces of apoptotic cells,

were polyreactive, and expressed unmutated IGHV. mAbs recognized two types of

antigens: native molecules located within healthy cells, which relocated to the

external cell surface during apoptosis; and/or neoantigens, generated by

oxidation during the apoptotic process. Some of the latter epitopes are similar

to those on bacteria and other microbes. Although most of the reactive mAbs were

not mutated, the use of unmutated IGHV did not bestow autoreactivity

automatically, since several such mAbs were not reactive. Particular IGHV and

IGHV/D/J rearrangements contributed to autoantigen binding, although the

presence and degree of reactivity varied based on specific structural elements.

Thus, clonal expansion in CLL may be stimulated by autoantigens occurring

naturally during apoptosis. These data suggest that CLL may derive from normal B

cells whose function is to remove cellular debris, and also to provide a first

line of defense against pathogens.

PMID: 19009014