The development and maintenance of B cell responses to microbial challenge

Abstract

Humoral responses are a critical component of the immune system and antibodies play an important role in the response to many pathogens. The work presented in this thesis examines the development, maintenance, and regulation of antibody production. T follicular helper (TFH) cells have been shown to provide B cell help in germinal centers (GCs). However, infection with T. gondii results in a loss of splenic organization, including the GCs. Thus, studies were performed to evaluate this splenic disorganization and the effects of this process on antibody responses. Furthermore, experiments to better understand the development of TFH cells revealed that TFH cells can arise from CD4+ T cells that have committed to the Th2 lineage in response to SEA immunization. However, aberrant B cell response can lead to antibody-mediated autoimmune disease, thus studies were conducted to further elucidate regulatory mechanisms to control GC responses. These revealed that IL-27 can inhibit GC responses through effects on TFH cells and directly through B cells. Finally, antibody responses are maintained long term through long-lived plasma cells in the bone marrow. Analysis of the Treg population in the bone marrow demonstrates a role for these cells in maintaining plasma cells, a relationship that can be transiently disrupted as both populations are lost during infection. Collectively, these studies highlight developmental processes and regulatory mechanisms that support B cell responses