CD22 and CD19 represent two specialized costimulatory or coreceptor cell surface molecules [PMID: 9476671, PMID: 9175829, PMID: 15364057, PMID: 9203413, PMID: 9047233] that also function as “response regulators” to modulate the intensity, quality, and duration of homeostatic and BCR‐induced signals [PMID: 9695183, PMID: 9695185]. Response regulators carry out broader functions than costimulatory molecules because they establish intrinsic signaling thresholds that provide a context for other transmembrane and cytoplasmic signals. CD22 is also a lectin‐like member of the Ig superfamily expressed exclusively by all mature B‐lineage cells, which binds ligands in vivo to regulate BCR and CD19 signal transduction, and provide essential survival signals.