Bonnie Dittel Laboratory

Senior Investigator Bonnie Dittel, PhD, studies cellular and molecular mechanisms involved in the regulation of inflammation, specifically multiple sclerosis.

Bonnie Dittel Laboratory Versiti Blood Research Institute

 

Research Interests | Immunobiology

The focus of our research program is to investigate cellular and molecular mechanisms involved in the regulation of inflammation. Inflammation is a component of virtually every disease and if not controlled can lead to severe tissue damage. The primary disease model utilized in the laboratory is the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). MS is an autoimmune disorder of the central nervous system (CNS) and is characterized by focal areas of inflammation. In past studies, we have extensively utilized EAE to study negative immune regulatory mechanisms that keep inflammation in check within the CNS.

Bonnie Dittel, PhD
Principal Investigator
Nancy Surdyk
Senior Administrative Assistant

B Cell IgD Low (BDL) 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.

 

Figure 1: An illustration of EAE disease in B cell deficient (BCD) mice. BCD mice (green dotted line) do not recover from the signs of EAE like their wild-type (WT (solid blue line)) counterparts. When BCD mice are adoptively transferred BDL (red line) prior to EAE induction, the mice undergo recovery similar to WT mice.

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

Figure 2: BDL induce Treg proliferation in a GITRL-dependent manner. BDL depicted in green including their cell surface phenotype engage CD4+Foxp3+ T regulatory (Treg) (blue) via GITRL, which binds to its receptor GITR on Treg thereby promoting their proliferation and expansion.

 

Thus, our findings indicate that BDL 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 BDL subset in mouse and humans.

BDL-based Adoptive Cell Therapy (ACT)

The ultimate goal of our research is to develop a BDL-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 BDL-based ACT will be generated and tested in humanized mouse models.

 

Figure 3: Strategy to generate a BDL-based universal adoptive cell therapy (ACT). To prevent allorecognition and rejection, expression of MHC class I and II molecules will be eliminated. To prevent NK killing of the MHC class II- cells, HLA-G will be expressed. To maintain survival of the ACT, an IgM+ parent cell will be selected. Overexpression of GITRL will promote Treg expansion. Redundant suicide mechanisms will be introduced to control the number of the BDL ACT after administration to patients.

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

2019-2021

R21AI145323, NIAID
A novel human regulatory B cell subset
Principal Investigator

2020-2021

Neuroscience Research Center Imagine More, Medical College of Wisconsin
Dynamics of B cell subtypes in multiple sclerosis before and after treatment
Co-investigator

2019-2022

RG-1901-33315, National Multiple Sclerosis Society
B Cell Regulation in EAE/MS
Principal Investigator

2020-2025

R01AI160244-01, NIAID- NIH Director’s Transformative Research Award
Development of a B cell therapeutic
Principal Investigator

 
Awards and Patents
Bonnie Dittel, PhD, has received a number of awards and patents for her research of autoimmune diseases like multiple sclerosis.
 
Datasets and Protocols
Dr. Dittel has published a number of datasets and protocols, including B cell subsets, RNA-seq data, cell populations and more.
 
Lab
Dittel lab personnel work in a collaborative environment and share knowledge to advance groundbreaking science.
 
News and Media
News and media highlights about Bonnie Dittel, PhD, including her research of multiple sclerosis at Versiti Blood Research Institute.
 
Publications
Dr. Dittel has been published in a number of prestigious scientific and medical journals for her study of autoimmune and inflammatory diseases.
 
Contact Us
Complete the contact us form to inquire about open lab positions or Dr. Dittel's research.
 
Bonnie N. Dittel, PhD
Dr. Dittel is a senior investigator at Versiti Blood Research Institute, whose research focuses on the underlying mechanisms of inflammation.
 
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