Maturation and Trafficking Markers on Rotavirus-Specific B Cells during Acute Infection and Convalescence in Children

Abstract

ABSTRACT We have previously studied B cells, from people and mice, that express rotavirus-specific surface immunoglobulin (RV-sIg) by flow cytometry with recombinant virus-like particles that contain green fluorescent protein. In the present study we characterized circulating B cells with RV-sIg in children with acute and convalescent infection. During acute infection, circulating RV-sIgD − B cells are predominantly large, CD38 high , CD27 high , CD138 +/− , CCR6 − , α4β7 + , CCR9 + , CCR10 + , cutaneous lymphocyte antigen-negative (CLA − ), L-selectin int/− , and sIgM + , sIgG − , sIgA +/− lymphocytes. This phenotype likely corresponds to gut-targeted plasma cells and plasmablasts. During convalescence the phenotype switches to small and large lymphocytes, CD38 int/− , CD27 int/− , CCR6 + , α4β7 +/− , CCR9 +/− and CCR10 − , most likely representing RV-specific memory B cells with both gut and systemic trafficking profiles. Of note, during acute RV infection both total and RV-specific murine IgM and IgA antibody-secreting cells migrate efficiently to CCL28 (the CCR10 ligand) and to a lesser extent to CCL25 (the CCR9 ligand). Our results show that CCR10 and CCR9 can be expressed on IgM as well as IgA antibody-secreting cells in response to acute intestinal infection, likely helping target these cells to the gut. However, these intestinal infection-induced plasmablasts lack the CLA homing receptor for skin, consistent with mechanisms of differential CCR10 participation in skin T versus intestinal plasma cell homing. Interestingly, RV memory cells generally lack CCR9 and CCR10 and instead express CCR6, which may enable recruitment to diverse epithelial sites of inflammation.