RelBcontaining

RelB-containing refers to transcription factor complexes that include the NF-κB subunit RelB. In vertebrates, NF-κB transcription factors form homo- and heterodimers that regulate immune and inflammatory genes. The RelB-containing dimers are mainly RelB:p52, formed in the noncanonical (alternative) NF-κB signaling pathway.

Activation of RelB-containing dimers is triggered by BAFF binding to BAFF-R, CD40 ligand engaging CD40, or lymphotoxin-β receptor signaling. These signals activate NF-κB-inducing kinase (NIK), which in turn activates IKKα. IKKα phosphorylates the NF-κB2 precursor p100, leading to its proteasomal processing to p52. RelB then dimerizes with p52, translocates to the nucleus, and binds κB sites to regulate genes involved in lymphoid organogenesis, B cell maturation, dendritic cell function, and chemokine expression.

The RelB-containing pathway is distinct from the canonical NF-κB pathway (RelA/p50) that is activated by a broad range of stimuli and relies on IKKβ and p65/p50 activity. Dysregulation of RelB-containing signaling has been implicated in immunodeficiency, autoimmunity, and certain lymphoid malignancies. RelB-containing dimers can be detected by methods such as EMSA or ChIP for RelB/p52. In animal models, RelB or NIK deficiencies yield impaired lymphoid organ development and disrupted splenic architecture, underscoring the pathway’s role in immune system organization.