Effect of CXCR5, PD-1 and ICOS on B-cell responses and relevance to myasthenia gravis
CLINICAL & TRANSLATIONAL IMMUNOLOGY, cilt.15, sa.6, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/cti2.70112
- Dergi Adı: CLINICAL & TRANSLATIONAL IMMUNOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Recep Tayyip Erdoğan Üniversitesi Adresli: Evet
Özet
Objectives T follicular helper (Tfh) cells regulate B-cell responses within germinal centres primarily via programmed cell death protein 1 (PD-1) and inducible T-cell costimulator (ICOS), whereas CXC chemokine receptor type 5 (CXCR5)-negative T peripheral helper (Tph) cells provide similar support extra-follicularly. Both subsets contribute to the pathogenesis of acetylcholine receptor-antibody-positive myasthenia gravis (AChR-MG). This study investigated the roles of PD-1, ICOS and CXCR5 in T-cell-mediated B-cell activation to identify therapeutic targets for MG.Methods CD4 T cells from 10 healthy controls and six untreated AChR-MG patients were sorted by CXCR5, PD-1 and ICOS expression, stimulated with anti-CD3/CD28, and co-cultured with autologous CD19 B cells. Plasmablast differentiation, total AChR-IgG and cytokine productions were measured.Results In healthy donors, PD-1+ or ICOS+ Tph cells modestly enhanced plasmablasts and IgG production, while CXCR5+ Tfh cells co-expressing PD-1 or ICOS induced significantly stronger B-cell responses. In AChR-MG patients, PD-1 expressing T cells promoted plasmablasts, antibody production and cytokine secretion regardless of CXCR5, with amplified effects in CXCR5+ co-cultures.Conclusions PD-1 expression on CD4+ T cells is associated with increased B-cell helper capacity. This effect is more pronounced in Tfh-related contexts and is linked to dysregulated humoral immune responses in MG. PD-1 appears to play a central role in the pathogenesis of MG, primarily through Tfh cell activity.