B Cell IgD Low (BD_L) Regulatory B Cells

B cell regulation of autoimmunity was first demonstrated by us in the EAE model, whereby B cell deficient (BCD) mice were unable to recover from the clinical signs of EAE.

In our subsequent studies, we discovered a new regulatory subset of B cells termed B Cell IgD Low (BD_L), named due to their low level of IgD expression. We found that adoptive transfer of BD_L into BCD promoted recovery from EAE. Specifically, BD_L negatively regulate the severity of EAE inducing CD4 Foxp3 T regulatory cells (Treg) expansion in a GITRL-dependent manner.

Thus, our findings indicate that BD_L play an essential role in Treg homeostasis whereby they maintain Treg numbers at a sufficient level to dampen inflammation. Current studies are investigating the development, phenotype and localization of this novel subset of regulatory B cells. These studies are being advanced using single cell RNA sequencing (scRNAseq), which we are utilizing to further define the BD_L subset in mouse and humans.

BD_L-based Adoptive Cell Therapy (ACT)

The ultimate goal of our research is to develop a BD_L-based universal ACT for the treatment of autoimmunity and other inflammatory disorders. To accomplish this goal, Dr. Dittel was recently awarded an NIH Director’s Transformational Research Award. The strategy is to develop a mouse prototype that escapes rejection by the immune system while potently increasing Treg cell numbers to achieve attenuation of EAE. Using knowledge gained from the mouse, a human BD_L-based ACT will be generated and tested in humanized mouse models.

Post-doc opportunities are available to work on BD_L focused projects. To express interest please contact Dr. Dittel at bdittel@versiti.org