The trajectory of human B‐cell function, immune deficiency, and allergy revealed by inborn errors of immunity

Abstract

SummaryThe essential role of B cells is to produce protective immunoglobulins (Ig) that recognize, neutralize, and clear invading pathogens. This results from the integration of signals provided by pathogens or vaccines and the stimulatory microenvironment within sites of immune activation, such as secondary lymphoid tissues, that drive mature B cells to differentiate into memory B cells and antibody (Ab)‐secreting plasma cells. In this context, B cells undergo several molecular events including Ig class switching and somatic hypermutation that results in the production of high‐affinity Ag‐specific Abs of different classes, enabling effective pathogen neutralization and long‐lived humoral immunity. However, perturbations to these key signaling pathways underpin immune dyscrasias including immune deficiency and autoimmunity or allergy. Inborn errors of immunity that disrupt critical immune pathways have identified non‐redundant requirements for eliciting and maintaining humoral immune memory but concomitantly prevent immune dysregulation. Here, we will discuss our studies on human B cells, and how our investigation of cytokine signaling in B cells have identified fundamental requirements for memory B‐cell formation, Ab production as well as regulating Ig class switching in the context of protective versus allergic immune responses.

Modulation of Immunity and Barrier Function in Pre- And Postnatal Animal Ontogenesis. Physiological Aspects of Natural Resistance in Sows

“…The peculiarity of all immunoglobulins is that their molecules have variable structuresdomains that bind to antigens. It should be noted that immunoglobulins are heterogeneous protein structures, as indicated by the different shapes of their different classes 75 .…”