Lecturer Søren E. Degn: “Many Nobel Prizes, a controversy, and a tale of how something good can go bad”

13.12.2019 | Zitta Glattrup Nygaard

Abstract

B cells are central to our ability to produce antibodies and mount humoral immunity. Few fields have garnered as much interest and been the focus of so many Nobel Prizes: from understanding how our immune system can react against practically anything, yet is tolerant of self, to harnessing the power of antibodies in the laboratory and the clinic.

The first step in the activation of B cells is the antigen-driven activation of the B cell receptor (BCR). Surprisingly, despite the fundamental importance of this process and years of intense scrutiny, there is long-standing controversy in the field about how this activation occurs. In the first part of my talk, I will provide new insights into this question based on experiments leveraging a novel nanoscaffold combined with a defined model antigen system, and taking into consideration antigen to BCR stoichiometry, antigen affinity and antigen avidity.

Once activated, B cells have the unique ability to undergo directed microevolution to drive a progressive increase in their antigen affinity. This occurs within secondary lymphoid tissues in induced microanatomical structures called germinal centers, in an elaborate process regulated by several subsets of specialized T helper cells. The germinal center reaction is requisite to our ability to generate high-affinity antibodies, but it is also involved in untoward reactions in autoimmune diseases. In the second part of my talk, I will discuss data from a novel mouse model of epitope spreading, demonstrating that autoreactive germinal center B cell responses are compartmentalized by T cell-MHCII restriction.

Taken together, our data highlight minimal antigen requirements of relevance to vaccine design, and point towards the potential of targeting limited sets of MHCII restricted T-cells in autoimmune disease.

The Biomedicine Seminar Series Organizing Committee
Line Reinert
Martin Thomsen
Søren Degn