Study of circulating plasmablasts in primary humoral response during human acute viral infection

Abstract

B cells provide several lines of immunity in host defense against viral infection, including the production of neutralizing antibodies. Following exposure to antigen, na"ive B cell differentiate into antibody-producing short-lived plasmablasts (PBs) and thus contribute to the first line of defense. With T cell help, some of B cells undergo a number of events, characterized by affinity maturation and isotype switching, lead to more specific immunity. Immunoglobulins (Ig) exist as distinct different classes, which are distinguished by structure of their constant region. In primary immune response, IgM is the first antibody to be produced before B cells have un-dergone affinity maturation, and thus it has been considered as a low affinity antibody than isotype-switched Ig such as IgG. In addition to its low binding affinity to antigen, the poly-reactivity of antibody, the ability to bind to various unrelated antigens, has been described in IgM. While B cells play a critical role in defense immunity through the production of antibodies, research on humoral immunity largely depend on serological study. Therefore, cellular analysis of antibody secreting cells (ASCs) still largely unexplored. Recently, research on ASCs during viral infection has shown that robust PB res-ponses were detected in peripheral blood. These studies reported that ASC responses in dengue or influenza virus infection were characterized by antigen specific, IgG-producing PBs. It is likely that these results represent sec-ondary response but not primary immune response since human adult usually have a history of encounter with these pathogen. Therefore, PB responses during acute phase of primary infection with virus re-main largely unexplored. In current study, we detected robust PB responses in the peripheral blood of patients with acute hepatitis A (AHA), which is an attractive disease to address the humoal responses in the primary acute viral infection. These PB responses were dominated by Ig...