The Germinal Center and T Regulatory Cells
Our laboratory has previously demonstrated that germinal center (GC) reactions in the murine spleen exhibit characteristics of a steady state reaction, including the process of isotype switching. At all time points during the splenic GC response, the ratio of IgM+ to switched GC B cells is steady. Of interest, GC reactions in the lymph node are regulated differently, with switching being dynamic rather than steady. As the response matures, IgM+ GC B cells diminish while switched GC B cells increase. To explore the regulatory elements that control GC reactions, we are testing whether neutralization of T regulatory cells (Tregs) alters switching within splenic and lymph node GCs. Additional projects will focus on determining the cellular targets of Tregs within the GC and the molecular means by which they effect their regulatory activity. Future experiments will determine if Tregs disruption will alter other processes of the GC such as affinity maturation and somatic hypermutation.
Alexander CM, Tygrett LT, Boyden AW, Wolniak KL, Legge KL, Waldschmidt TJ. T regulatory cells participate in the control of germinal centre reactions. Immunology. 2011 Aug;133(4):452-68. doi: 10.1111/j.1365-2567.2011.03456.x. Epub 2011 Jun 3. PubMed PMID: 21635248; PubMed Central PMCID: PMC3143357.
Verma S, Alexander CM, Carlson MJ, Tygrett LT, Waldschmidt TJ. B-cell studies in chronic ethanol mice. Methods Mol Biol. 2008;447:295-323. PubMed PMID:18369926.