Effect of CXCR5, PD‐1 and ICOS on B‐cell responses and relevance to myasthenia gravis
Merve Çebi, Arman Çakar, Hacer Durmuş, Yeşim Parman, Güher Saruhan‐DireskeneliAbstract
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.