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- Title
TACI expression and plasma cell differentiation are impaired in the absence of functional IκBNS.
- Authors
Khoenkhoen, Sharesta; Erikson, Elina; Ádori, Monika; Stark, Julian M; Scholz, Jean L; Cancro, Michael P; Pedersen, Gabriel K; Karlsson Hedestam, Gunilla B
- Abstract
Impaired classical NF‐κB pathway signaling causes reduced antibody responses to T‐independent (TI) antigens. We investigated the potential reasons for defective TI responses in mice lacking the atypical inhibitory kappa B (IκB) protein of the NF‐κB pathway, IκBNS. Analyses of the plasma cell compartment in vitro and in vivo after challenge with lipopolysaccharide (LPS) showed significant decreases in the frequencies of plasma cells in the absence of IκBNS. In vitro activation of B cells via the B cell receptor or via Toll‐like receptor 4 revealed that early activation events were unaffected in IκBNS‐deficient B cells, while proliferation was reduced compared to in similarly stimulated wildtype (wt) B cells. IκBNS‐deficient B cells also displayed impaired upregulation of the transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), which is essential for TI responses, and decreased sensitivity to TACI ligands upon stimulation. Furthermore, IκBNS‐deficient B cells, in contrast to wt B cells, displayed altered expression of IRF4, Blimp‐1 and Pax5 upon LPS‐induced differentiation, indicating impaired transcriptional regulation of plasma cell generation.
- Subjects
PLASMA cells; ANTIBODY formation; LIPOPOLYSACCHARIDES; NF-kappa B; B cells
- Publication
Immunology & Cell Biology, 2019, Vol 97, Issue 5, p485
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1111/imcb.12228