-
Views
-
Cite
Cite
Adesola C Olatunde, Patrice N Mimche, Spencer O Seely, Taryn P Stewart, Tracey J Lamb, Ephrin B receptor tyrosine kinase ligands modulate the germinal center reaction and control humoral immune responses to malaria, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 190.29, https://doi.org/10.4049/jimmunol.202.Supp.190.29
Close - Share Icon Share
Abstract
Malaria remains a global health priority causing half a million deaths annually. Protective antibody responses that can control the Plasmodium parasites that cause malaria are an essential component of naturally acquired immunity and develop after years of continuous exposure to Plasmodium parasites. The protective humoral response is short-lived and tends to wane in the absence of parasite re-infections. The cellular and molecular mechanisms that prevent the development of long-lived humoral immunity against malaria remain poorly understood. Recently, ephrin B1, a ligand for the Eph B receptor tyrosine kinase subfamily, was shown to be involved in T follicular helper (Tfh) cell recruitment, retention and contact-dependent interaction with germinal center (GC) B cells, key processes in the production of efficacious antibody responses. We hypothesize that EphB/EphrinB signaling pathway is required for the development of Plasmodium humoral responses. Using a non-lethal P. yoelii XNL infection model, we observed an upregulation in the expression of Ephrin B on both GC B cell and Tfh cells at the peak of the infection in wild type mice. Selective deficiency of Ephrin B1/B2 on B cells (CD19cre+ Ephrin B1/B2fl/fl mice) led to lethality in some mice infected with an otherwise non-lethal P. yoelii XNL infection. On the other hand mice that lack the expression of Ephrin B1/B2 on T cells (CD4cre+ Eprhin B1/B2fl/fl mice) were able to control P. yoelii XNL infection. Our data show a requirement for Ephrin B1/B2 signaling on B cells for an effective contact-dependent interaction with Tfh cells and for optimal antibody responses during Plasmodium infection.
