Circulating Plasmablasts With A Bone Marrow Phenotype Secrete Non-Specific Igm In Acute Hepatitis A

Background: The antigen-specificity and phenotypes of Antibody-secreting cells (ASCs) have not been studied during a primary acute viral infection. We investigated the nature of ASCs here by direct ex vivo assays in patients with acute hepatitis A (AHA) which is caused by the primary infection of hepatitis A virus (HAV). Methods & Materials: The study included 39 patients diagnosed with AHA infection who were hospitalized at Chung-Ang University Hospital. All patients were seropositive for anti-HAV IgM, and all had clinical features of acute hepatitis. Peripheral blood samples at the acute stage were collected on the day of admission from all of the 39 patients. Follow-up sampling was performed at the subacute stage (5-14 days) or at the convalescent stage (35-150 days). Serum levels of the total IgM, IgG and the subisotype of IgG were measured by a CBA assay. ELISpot filter plates were coated overnight with anti-human Ig to detect the total IgM or IgG-secreting ASCs. Results: A robust plasmablast response was detected in peripheral blood during the acute stage and was dominated by IgM secretion. It was demonstrated that a substantial portion of the response was non-virus-specific in the study of the plasmablasts and the secreted IgM. We detected HAV-specific plasmablasts by staining with fluorochrome-tagged VP1 protein and compared them with non-HAV-specific plasmablasts. Non-HAV-specific plasmablasts have the phenotype of Ki-67low/CD138high/CD31high/CD38high as compared with HAV-specific plasmablasts, demonstrating that non-HAV-specific plasmablasts have a bone marrow (BM) plasma cell-like phenotype while HAV-specific plasmablasts have a typical phenotype of circulating plasmablasts. Conclusion: These data suggest that non-HAV-specific plasmablasts are mobilized ASCs from the BM niches of plasma cells, whereas HAV-specific plasmablasts are newly generated ASCs. In this study, we demonstrated that pre-existing BM plasma cells are released to circulation during AHA and contribute to the non-virus-specific ASC response and IgM secretion.