title: Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect.
abstract: Surges of serum Abs after immunization and infection are highly specific for the offending Ag, and recent studies demonstrate that vaccines induce transient increases in circulating Ab-secreting cells (ASCs). These ASCs are highly enriched but not universally specific for the immunizing Ag, suggesting that a fraction of these ASCs could arise from polyclonal bystander stimulation of preexisting memory cells to unrelated Ags. This model is proposed to explain maintenance of long-lived serological memory in the absence of Ag exposure. To test this model, we measure the ability of respiratory syncytial virus and influenza virus infection or immunizations to influenza virus, tetanus toxoid, hepatitis B Ag, and human papillomavirus to stimulate bystander memory cells specific for other major environmental Ags that represent a large fraction of the preexisting memory B compartment. Bystander or nonspecific ASC responses to respiratory syncytial virus and tetanus could not be detected above the background levels in healthy adults, despite the presence of circulating memory B cells specific for the corresponding Ags. Nonspecific ASC responses in the healthy subjects and cord blood samples were similar. In contrast, both vaccination and infection induce massive expansion of circulating Ag-specific ASCs without significant increases in the frequencies of ASCs against unrelated Ags. Hence, nonspecific stimulation of memory B cells is unlikely to contribute to the mechanisms of long-term serological memory against major human pathogens. Additionally, high specificity of circulating ASCs after antigenic challenge highlights the diagnostic value of interrogating ASCs as an ideal single-time-point diagnostic immune surrogate for serology during acute infection.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. eunhyung_lee@urmc.rochester.edu
authors: F Eun-Hyung
authors: FE
authors: Lee
authors: Jessica L
authors: JL
authors: Halliley
authors: Edward E
authors: EE
authors: Walsh
authors: Andrew P
authors: AP
authors: Moscatiello
authors: Brittany L
authors: BL
authors: Kmush
authors: Ann R
authors: AR
authors: Falsey
authors: Troy D
authors: TD
authors: Randall
authors: Denise A
authors: DA
authors: Kaminiski
authors: Richard K
authors: RK
authors: Miller
authors: Iñaki
authors: I
authors: Sanz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000921:Antibody-Producing Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination; D014777:Virus Diseases / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral