Aberrant B-cell signaling in active cGVHD. B cells in cGVHD exhibit increased constitutive signaling through Erk and Akt that is also associated with decreased levels of proapoptotic Bim. Aberrant BAFF-associated signaling is associated with a heightened metabolic state and resistance to apoptosis. Constitutive BCR-associated signaling in cGVHD B cells is associated with increased responsiveness to surrogate antigen ex vivo, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. After initiation of BCR signaling, cGVHD B cells exhibited increased BLNK and Syk phosphorylation compared with B cells from patients without cGVHD. Shaded pathways are common to BAFF and BCR signaling. Unshaded pathways are specific for BCR signaling.