BAFF-R stimulation triggers persistent RelB and cRel activity to control in vitro survival functions. (A) BAFF, which binds TACI and BAFF-R, is a key regulator of peripheral B-cell maintenance. BAFF-R signaling functions occur primarily in an NIK-dependent, noncanonical NF-κB manner, mediated through RelB activity, whereas TACI triggers NEMO-dependent canonical NF-κB. (B) Identification of activated NF-κB species in B cells stimulated with BAFF for 24 hours by supershift analysis. (C) RelA, RelB, and cRel EMSA (see “Materials and methods”) of B cells are used to reveal their respective activity kinetics following BAFF-R perturbation. (D) Quantification of RelA, RelB, and cRel activities of BAFF-stimulated primary B cells derived from EMSA. Naive is resting, unstimulated B cells; early and late activity correspond to activities following 1 to 5 hours and 24+ hours of BAFF stimulation, respectively. Representative of ≥4 experiments. *P < .05; **P < .01. (E) Summary table of known NF-κB–deficient mouse models and the effect on B-cell populations. Gray boxes denote a B-cell developmental defect. +++, cell numbers equate to typical wild-type level; ++++, greater than wild-type; ++, intermediate level; +, low; -, not present. EMSA for panels B-C representative of at least 3 experiments.