THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Better understanding of B cell/T cell interaction could lead to new treatment targets

Communications between B cells and T cells have a fundamental role in autoantibody production, and an educational session at ACR Convergence 2020 will review how follicular T helper cells, germinal center B cells, and plasma cells impact autoimmune disease.

The initial presentation of B Cell and T Cell Convergence for Autoantibody Neogenesis will take place on Sunday, Nov. 8 from 11 a.m. – 12 p.m. EST and feature a live question-and-answer session in addition to three presentations. Registered annual meeting attendees also can access the session on demand until March 11, 2021.

Jeremy Boss, PhD, professor and chair, Department of Microbiology & Immunology, Emory University School of Medicine, will discuss research done by his group with the Ignacio Sanz lab that was published last winter in Nature Immunology (Scharer, C.D., Blalock, E.L., Mi, T. et al. Epigenetic programming underpins B cell dysfunction in human SLE). With a small cohort of nine African American female patients, some with systemic lupus erythematosus and others as a control group, researchers did an extensive epigenomics and transcriptomics study on multiple subsets of peripheral B cells.

Using DNA methylation, chromatin accessibility, and transcription to analyze each subset, researchers tried to determine the mechanisms that underpin the disease caused by these B cells. Dr. Boss said that the Sanz group showed that two subsets, activated naïve and DN2 B cells, produced autoantibodies in greater numbers in those with SLE versus the healthy control group.

“It was sort of a surprise, and a major finding,” Dr. Boss said. “We did not expect that the naïve cells would have an epigenetic signature that are hallmarks of pathogenic DN2 cells.”

This comprehensive analysis was the first of its kind for providing this kind of detail about these cell types, Dr. Boss noted, and will help improve what is today a poor understanding about the etiology of autoimmune diseases.

“While we don’t have answers for all the questions we can come up with, we sort of have a platform now to begin to explore various genes and transcriptional mechanisms of control that could potentially open up new targets for therapy,” he said. “Certainly, if we can ever move the markers to diagnostic assays, we might be able to better predict disease outcome. SLE is all about flares. Patients go through cycles, and we analyzed our patients while they were flaring.”

Pamela Schwartzberg, MD, PhD, National Institutes of Health, will open the session with a discussion of the role of follicular T helper cells. Dr. Schwartzberg’s lab focuses on signaling pathways in T lymphocytes and on pathways affected by primary immunodeficiencies and how they affect T cell development and functional responses. Paolo Casali, MD, Ashbel Smith Professor and distinguished research professor of medicine, microbiology, immunology & molecular genetics, University of Texas Long School of Medicine, will present on epigenic regulation of AID and the autoantibody response by the histone deacetylase sirt1.