David Rothstein
University of Pittsburgh, PA·Microbiology & Immunology
B cells are best known for making antibodies, but they can also steer immune responses in other ways. Some, called regulatory B cells (Bregs), calm the immune system.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
- Topics
regulatory B cells
Bregs
effector B cells
- Grants
- 2 known grants, through Apr 2029
What they work on
- Define the gene activity of TIM-4+ effector B cells and the signaling pathways, including IL-23 and IL-17, that switch on their inflammatory program while suppressing IL-10 and regulatory function, using RNA sequencing and quantitative PCR.
- Identify transcription factors, such as RORγt, that control the inflammatory set of signals made by TIM-4+ effector B cells.
- Determine in mouse transplant models how TIM-4+ effector B cells drive rejection, including roles of antigen specificity, plasma cells and B cell IL-17 targets, and test whether IL-23 blockade prolongs graft survival.
- Test whether IL-10+ or TIM-1+ regulatory B cells from follicular, marginal zone and plasma cell groups control different aspects of immunity, using IL-10-GFP reporter mice.
- Determine how BLIMP-1, plasma cells and the microbiota interact to regulate regulatory B cell numbers, using mice with B cell-specific BLIMP-1 deletion that show better graft survival and milder EAE.
More about the research
Others, called effector B cells (Beff), fuel inflammation. This split may explain a puzzle in medicine. Drugs that deplete B cells can quickly improve autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, yet the same approach around the time of transplant can worsen kidney and heart transplant rejection. The lab argues that treatments could work better if they could target Bregs and Beff separately, which requires knowing how to identify each type and what controls it. Its two grants study each side of this balance in mouse models of transplantation and autoimmunity.
Why it matters
Transplant recipients risk organ rejection, and people with autoimmune diseases suffer immune attack on their own tissues. Current B cell-depleting drugs remove both calming and inflammatory B cells, with mixed results. By defining markers and controls for each type, this work could guide treatments that expand Bregs or block Beff, for example through IL-23 blockade, to prolong transplanted organ survival and limit autoimmunity.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Igal Ifergan
University of Cincinnati, OH·Microbiology & Immunology
Characterize mature (CD27- CD11b+) and immature (CD27+ CD11b-) natural killer cell subsets in the brain and spinal cord across stages of relapsing-remitting EAE, a mouse model of MS, using single-cell RNA sequencing.
Laurie Harrington
University of Alabama at Birmingham, AL·Microbiology & Immunology
Determine how the transcription factor STAT4 directs the accumulation of Th17 cells, a pro-inflammatory CD4 T cell subset, in inflamed peripheral tissues.
Mandy J Mcgeachy
Cornell University, NY·Microbiology & Immunology
Determine how the interaction between PIP5K1a, an enzyme making the nuclear lipid PIP2, and ARS2, an mRNA cap-binding protein, is regulated as Th17 cells differentiate, using primary human T cells and CD28-humanized CD28A210P mice.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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