Differences in Self-Recognition between Secreted Antibody and Membrane-Bound B Cell Antigen Receptor

The random gene segment rearrangement during B cell development ensures Ab repertoire diversity. Because this process might generate autoreactive specificities, it has been proposed that stringent selection mechanisms prevent the development of autoreactive B cells. However, conventional assays to identify autoreactive B cells usually employ in vitro-generated Abs, which differ from membrane-bound BCRs. In this study, we used a cell-based assay to investigate the autoreactivity of membrane-bound BCRs derived from different B cell developmental stages of human peripheral blood. Contrasted to soluble Ab counterparts, only a few of the tested BCRs were autoreactive, although the cell-based assay sensitively detects feeble Ag recognition of a germline-reverted murine BCR that was selected after OVA immunization of mice, whereas conventional assays failed to do so. Together, these data suggest that proper identification of autoreactive B cells requires the membrane-bound BCR, as the soluble Ab may largely differ from its BCR counterpart in Ag binding.