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Persistent virus infections with non- or poorly cytopathic viruses are commonly associated with B cell dysregulations. These include the induction of hypergammaglobulinemia and the emergence of virus-unspecific antibodies. These seemingly unspecific antibody responses interfere with the virus-specific humoral immunity and contribute to delayed virus control. Whether these virus-unspecific antibodies are induced in the B cell follicle or at extrafollicular sites and whether one specific CD4 T cell subset is involved in the polyclonal B cell activation is unclear. Here we studied virus-unrelated IgG antibody responses against self or foreign antigens in the context of persistent lymphocytic choriomeningitis virus (LCMV) infection. We found that the LCMV-unspecific antibody response is short-lived and induced predominantly at extrafollicular sites and depends on the presence of LCMV-specific CD4 T cells. Our data support a scenario in which activated, virus-specific CD4 T cells provide help to non-specific B cells at extrafollicular sites, supporting the production of virus unspecific IgG antibodies during persistent viral infection.

Original publication




Journal article


Eur j immunol

Publication Date





396 - 403


B cells, CD4 T cells, LCMV, chronic infection, polyclonal B cell activation