Dr. Shiv Pillai provides a historical perspective on the current model of 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 of 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.
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… Continue Reading