title: Rotavirus differentially infects and polyclonally stimulates human B cells depending on their differentiation state and tissue of origin.
abstract: We have shown previously that rotavirus (RV) can infect murine intestinal B220(+) cells in vivo (M. Fenaux, M. A. Cuadras, N. Feng, M. Jaimes, and H. B. Greenberg, J. Virol. 80:5219-5232, 2006) and human blood B cells in vitro (M. C. Mesa, L. S. Rodriguez, M. A. Franco, and J. Angel, Virology 366:174-184, 2007). However, the effect of RV on B cells, especially those present in the human intestine, the primary site of RV infection, is unknown. Here, we compared the effects of the in vitro RV infection of human circulating (CBC) and intestinal B cells (IBC). RV infected four times more IBC than CBC, and in both types of B cells the viral replication was highly restricted to the memory subset. RV induced cell death in 30 and 3% of infected CBC and IBC, respectively. Moreover, RV induced activation and differentiation into antibody-secreting cells (ASC) of CBC but not IBC when the B cells were present with other mononuclear cells. However, RV did not induce these effects in purified CBC or IBC, suggesting the participation of other cells in activating and differentiating CBC. RV infection was associated with enhanced interleukin-6 (IL-6) production by CBC independent of viral replication. The infection of the anti-B-cell receptor, lipopolysaccharide, or CpG-stimulated CBC reduced the secretion of IL-6 and IL-8 and decreased the number of ASC. These inhibitory effects were associated with an increase in viral replication and cell death and were observed in polyclonally stimulated CBC but not in IBC. Thus, RV differentially interacts with primary human B cells depending on their tissue of origin and differentiation stage, and it affects their capacity to modulate the local and systemic immune responses.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, 300 Pasteur Dr., Alway Bldg, Rm M121, Stanford, CA 94305, USA.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Narváez
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Franco
authors.forename: Juana
authors.initials: J
authors.lastname: Angel
authors.forename: John M
authors.initials: JM
authors.lastname: Morton
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016923:Cell Death; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D012401:Rotavirus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015850:Interleukin-6; D016209:Interleukin-8