AI Article Synopsis

  • Influenza virus infection triggers strong B cell responses that provide long-term immunity, primarily through T-dependent mechanisms involving follicular T helper cells.
  • This study highlights that ICOS, rather than CXCR5, identifies T cells that help B cells during influenza infection, and it distinguishes a specific subset of germinal center T cells based on their unique markers.
  • The research suggests that the presence of CXCR4- and CXCR5-coexpressing CD4 helper cells is crucial for effective antiviral B cell immunity, differing substantially from T cell responses seen in autoimmunity.

Article Abstract

Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide lifelong humoral immunity against the homotypic virus strain. Follicular T helper cells (T(FH)) are key regulators of humoral immunity. Questions remain regarding the presence, identity, and function of T(FH) subsets regulating early extrafollicular and later germinal center B cell responses. This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity induced by influenza virus infection and identifies germinal center T cells (T(GC)) as lymph node-resident CD4(+) ICOS(+) CXCR4(+) CXCR5(+) PSGL-1(lo) PD-1(hi) cells. The CXCR4 expression intensity further distinguished their germinal center light and dark zone locations. This population emerged strongly in regional lymph nodes and with kinetics similar to those of germinal center B cells and were the only T(FH) subsets missing in influenza virus-infected, germinal center-deficient SAP(-/-) mice, mice which were shown previously to lack protective memory responses after a secondary influenza virus challenge, thus indicting the nonredundant functions of CXCR4- and CXCR5-coexpressing CD4 helper cells in antiviral B cell immunity. CXCR4-single-positive T cells, present in B cell-mediated autoimmunity and regarded as "extrafollicular" helper T cells, were rare throughout the response, despite prominent extrafollicular B cell responses, revealing fundamental differences in autoimmune- and infection-induced T-dependent B cell responses. While all ICOS(+) subsets induced similar antibody levels in vitro, CXCR5-single-positive T cells were superior in inducing B cell proliferation. The regulation of T cell localization, marked by the single and coexpression of CXCR4 and CXCR5, might be an important determinant of T(FH) function.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416343PMC
http://dx.doi.org/10.1128/JVI.06904-11DOI Listing

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