The functional antigen reactivity underlies the biological and clinical behavior of the CLL clone. Chu and colleagues report that several CLL monoclonal antibodies (mAbs) can bind MYHIIA-exposed apoptotic cells (MEACs), although not all recognize MYHIIA (ie, the molecular targets of different CLL mAbs may be other autoantigens exposed on MEACs during apoptosis). MEAC binding was essentially a property of CLL monoclonal antibodies (mAbs) with unmutated IGHV genes. Intriguingly, MEAC binding was identified as a stronger predictor of survival than IGHV gene mutational status. This might imply that the functional antigen reactivity profile rather than the presumed antigen-binding site structure shaped by somatic hypermutation underlies the biological behavior of the CLL clone, eventually determining patient prognosis. MEAC binding was also found to be consistent between CLL mAbs from cases in subsets with stereotyped IGs, strongly indicating that clustering of CLL cases into distinct subsets based on stereotyped primary IG gene sequences is functionally relevant. MEACs indicates MYHIIA-exposed apoptotic cells; MYHIIA, non-muscle myosin heavy chain IIA; antigens, vimentin, filamin B, oxidized epitopes, etc; ⊠, no MEACs binding; , MEACs binding; #, number of stereotyped subset.