Research Mission

The Erickson Lab investigates how the immune system is controlled leading to the production of antibodies. A key research goal is to test the therapeutic potential of targeting these immune mechanisms to promote antibody protection in health and prevent antibody pathogenicity in autoimmune and allergic diseases.

Research Description

The Erickson Lab uses an integrative approach including high-dimensional phenotypic and functional analysis of single cells, in vivo and ex vivo genetic, proteomic, and imaging techniques for studying how the immune system regulates antibody production and function, in health and disease.

B cells recognize molecules expressed by microbes that results in immune protection mediated through the production of antibodies. These antibodies protect the host from infection by multiple functions including neutralization, facilitating phagocytosis of the microbe, and triggering inflammation through the activation of soluble factors. However, unwanted B cell responses occur in certain diseases that lead to antibodies that can cause chronic inflammation and therefore contribute to pathogenesis including systemic lupus erythematosus (SLE) and food allergy. The underlying immune mechanisms controlling these unwanted B cell responses are poorly understood. A central focus of our lab is to address this knowledge gap using an iterative approach between mouse and human studies to identify potential human pathways of pathogenic antibody production in chronic inflammatory diseases.

1. Understanding antibody development and function in autoimmunity:

   How are antibodies released from B cells and what impact does this have in mediating intercellular communication and inflammation? How are antibodies deposited in different tissue sites and does this confer distinct functions?

   We study systemic lupus erythematosus (SLE) that is an autoimmune disease characterized by the breakdown of immune tolerance and the production of autoreactive antibodies that form immune complexes (ICs), which trigger inflammation and lead to tissue damage. Despite clear evidence linking ICs to the pathogenesis of SLE, identification of how ICs form and the factors that influence IC localization and pathogenicity in tissues has remained elusive. Our preliminary studies demonstrate that activated B cells secrete extracellular vesicles (EVs) that express antigen-specific surface IgG and bind antigen. Moreover, we have identified circulating IgG+ EVs from lupus-prone mice that bind nuclear self-antigens, are taken up by neutrophils, and localize to the kidney. Recent studies of SLE patients have also identified circulating EVs that co-express IgG and nuclear antigens on their surface which correlate with increased antinuclear antibody titers in whole plasma. Based on these data, we propose a novel hypothesis that IgG-expressing EVs released by activated B cells upregulate inflammatory pathways either directly (i.e., as an IC), or indirectly by interacting with a variety of cells of the innate immune system that then contribute to the pathogenesis of lupus. We are testing this hypothesis using a novel reporter mouse strain that allows for the in vivo tracking, isolation, and functional interrogation of EVs derived from class-switched IgG+ B cells. Our long-term goal is to investigate B cell-derived EVs in mediating intercellular communication, regulating deleterious host immune responses in SLE, which may provide new therapeutic strategies to reduce inflammation and tissue injury.

2. Understanding antibody development and function in allergy:

   What are the molecular and cellular signals that cause sensitization leading to the development of allergy and what role, if any, do signals from microbes play in this process?

   Allergies rank among the sixth leading cause of chronic human diseases in the United States and affect more than 50 million Americans each year. Food allergy is a growing public health concern that can carry a high risk of life-threatening allergic reactions. Our lab studies a novel food allergy called alpha-gal syndrome (AGS; also known as red meat allergy) that develops worldwide in adults who have tolerated meat consumption for years and is linked to tick bites through mechanisms that remain unknown. In the United States, bites from lone star ticks can induce IgE antibodies to the oligosaccharide galactose--1,3-galactose (-gal), a blood group antigen of non-primate mammals and therefore is present in mammalian-derived food products (i.e., beef, pork and lamb; dairy; drugs). -gal is also found within certain tick species. We use mouse and human studies of AGS to identify the underlying host immune mechanisms by which skin exposure to ticks leads to the development and maintenance of IgE production.