T-regulatory cells and IL-10 are important in maintaining control of germinal center reactions (89.29)

Autor: Carla-Maria Alexander, Thomas Waldschmidt
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Immunology. 182:89.29-89.29
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.182.supp.89.29
Popis: Previous work from our laboratory demonstrated the primary splenic germinal center (GC) reaction to display traits of a steady state, especially in regards to the ratio of IgM+ to switched GC B cells. The GC is a site of intense proliferation, class switching, apoptosis and selection, and as such must have strict regulation. Studies in our laboratory have shown that T regulatory cells (T-regs) play a pivotal role in regulation of the GC, as steady state dynamics were disrupted when T-regs were depleted or dysregulated by anti-CD25 and anti-GITR, respectively. Current studies are exploring the mechanism by which T-regs exert their control within the GC. Based on previous reports studying the means by which T-regs suppress their targets, we have tested whether granzyme B, perforin, Fas and IL-10 contribute to the homeostasis of GC responses. GC reactions in granzyme B-/-, perforin-/-, and B6.lpr mice were found to be normal after immunization, demonstrating that the granzyme B/perforin and Fas/Fas ligand pathways are unlikely to play a central role in controlling GCs. Treatment with a blocking anti-IL-10R mAb did result in loss of GC control however, suggesting that T-regs may be utilizing this cytokine to maintain the balance of IgM+ to switched B cells within the GC. Studies are continuing to determine if T-regs and IL-10 also affects other elements of B cell differentiation including affinity maturation and memory.
Databáze: OpenAIRE