Shiv Pillai (Harvard) 1: Early B Cell Development: A Look at the Defining Questions in Immunology

Video Description

https://www.ibiology.org/immunology/b-cell-development/ Shiv Pillai provides a historical perspective on the steps that led to formulate today’s model on how the immune system works and outlines the underpinnings of B cell development. Talk Overview: Dr. Shiv Pillai provides a historical perspective on the steps that led to formulate today’s model on how the immune system works. Scientists observed that the body produces molecules (antibodies) that recognize the entry of foreign particles (antigens). He outlines the different models of the structure and functions of antibodies and explains the process by which antibody diversity is generated during B cell development (VDJ recombination). B cell development also involves two checkpoints to ensure the generation of functional antibodies and prevent the recognition of self-structures. In his second lecture, Pillai explains how earlier in his career he discovered that two surrogate light chains bind to the heavy chain in pre-B cells to create the pre-B cell receptor (pre-BCR). He showed that binding of the surrogate chains facilitates the formation of the pre-BCR that is needed for B cell development. Pillai demonstrated that the pre-BCR signals through Bruton Tyrosine Kinase (Btk). Patients with non-functional Btk manifest signs of immunodeficiency and deficiency of B-cells in the blood, which shows the importance pre-BCR signaling for proper B-cell development. In his third lecture, Pillai explains IgG4-Related Disease (IgG4-RD), a chronic inflammatory condition characterized by elevated numbers of T cells and IgG4 secreting plasma cells in the affected tissue. Using tissue samples from patients with the disease, his laboratory isolated and characterized the CD4+ T cells associated with IgG4-RD. Furthermore, he explains how the crosstalk between these CD4+ T cells and B cells is important for IgG4-RD development, and showed that depletion of B cells improves the outcome of the disease.   Speaker Biography: Dr. Shiv Pillai is a professor of medicine and health sciences and technology at Harvard Medical School, and a Ragon Institute investigator. Pillai completed his medical studies at Christian Medical College Vellore, India (1976), and subsequently obtained his doctorate in biochemistry at Calcutta University, India. He continued his postdoctoral training at David Baltimore’s lab at MIT (1984-1988). It was at Baltimore’s lab where Pillai discovered the existence and importance of surrogate light chains for B cell development. The surrogate light chains bind the antibody heavy chain in pre-B cells (immature B cells), and form the pre-B cell receptor (pre-BCR). The signaling of pre-BCR is crucial for proper B-cell development. In 1988, he joined the faculty of Massachusetts General Hospital and Harvard Medical School. Today, his lab continues to study the basis of the immune system in order to provide further understanding to human disease. Learn more about Pillai’s research at his lab website: http://www.ragoninstitute.org/portfolio-item/pillai