Bringing together members of the bio community interested in and doing research in immunoengineering.

"Deciphering Gene Regulatory Mechanisms of B cells with implications for COVID-19"

Maggie Brown
Graduate Student - Greg Gibson, Ph.D., Advisor
Georgia Tech

ABSTRACT
B cells play a critical role in the immune system by creating antibodies which neutralize pathogenic viruses and bacteria. Studies describing B cell subsets have defined each population with surface markers and bulk transcriptomic or bulk ATAC methods. While single cell studies have become more prevalent, little is known about how these B cell subsets are transcriptionally and epigenetically distinct. I report a high-resolution definition of gene regulatory profiles of ASCs and DN2 cells by combining single cell transcriptomic and epigenetic data to determine the core transcriptional programs which define these populations. Additionally, I ask whether joint transcriptomic and epigenetic profiling can elucidate the individual variability of B cells in the immune system and how they respond to infection, specifically COVID-19 infection. COVID-19 has shown to affect individuals in different ways, with some recovering asymptomatically, experiencing mild symptoms, or severe symptoms resulting in hospitalization and even fatality. Recent studies have shown increased pro-inflammatory responses in severe COVID-19 PBMC coupled with a lack of interferon response, however, specific mechanisms of how B cells contribute to mild or severe cases of COVID-19 is still unknown. To expand on these ideas and further describe a baseline B cell differentiation path from naïve to ASCs, I utilize transcriptomic and epigenetic profiling of B cells to elucidate novel and detailed mechanisms of the roles they play in the variable severity of immune response to infection.

"A Pan-tissue Single-cell Atlas of Human B Cells in Healthy and Disease States"

Erin Connolly
Graduate Student - Greg Gibbson, Ph.D., Advisor
Georgia Tech

ABSTRACT
B cells are one of the most unique and versatile populations of cells in the body, playing a key role in humoral immunity and in modulating immune cell behavior in tumors and chronically inflamed tissues. While functioning as the most prolific protein secretion factories, B cells also traffic to tissues in a targetable fashion and can engraft for decades. B cells’ rich biology and intrinsic properties offer unique opportunities for engineering vaccines or therapies to recruit B cells and boost immune defenses. Recent studies have explored the considerable B cell heterogeneity within tissues, however, characterization of B cells at single-cell resolution across tissues in healthy and diseased organs remains limited. In this study, we constructed a B cell atlas by integrating single-cell transcriptomic data from ~1M B cells across 2k donors, 16 tissues, and 24 disease states. We uncovered ubiquitous B cell subtypes, tissue-specialized B cells and disease-activated B cell populations. These data demonstrate a transcriptional signature showing increased age is associated with declining naïve and increasing senescent B cell populations. Unexpectedly, supercentenarians, rare subjects who reach ≥ 110 years while staying healthy, have an abundance of a rare long-lived (SDC1+) plasma cell type with cytotoxic features, suggesting that the reprogramming of plasma cells towards enhanced cytotoxic ability may be associated with increased longevity. We identified an extra-follicular DN2 B cell cluster (marked by TBX21 and CXCR3) uniquely expanded in the blood and disease-specific tissue of four distinct autoimmune and proinflammatory disorders (i.e. CSF in multiple sclerosis patients and synovial fluid in rheumatoid arthritis patients) laying the groundwork for therapeutic approaches limiting DN2 cell trafficking. Altogether, our cross-tissue and pan-disease approach highlights the importance of a holistic view of the environment in which B cells mature, traffic, and function to provide new insights into B cell immunity and foster novel B cell therapies for clinical applications. 

Upcoming Immunoengineering Trainee Seminars - Spring 2022
April 15 - Maggie Manspeaker (Thomas Lab) and Fredrick Bulondo (Babensee Lab)

The goal of this series is to enhance our Immunoengineering community here at Georgia Tech and to include involvement from Emory participants at regular intervals. Seminars will feature one or two research presentations by graduate students and postdoctoral fellows, followed by lively discussion.

If you have any questions or are interested in being a speaker, please contact Karen Martin, Abir Muhuri, or Belinda Joseph. Thanks!