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B cells delay neutrophil migration toward the site of stimulus: tardiness critical for effective bacillus Calmette-Guérin vaccination against tuberculosis infection in mice. | LitMetric

AI Article Synopsis

  • Mutations in the btk gene lead to X-linked immune deficiency, primarily affecting B lymphocyte function and reducing the effectiveness of BCG vaccination against tuberculosis in CBA/N-xid mice.
  • The study reveals that B cell deficiency causes increased neutrophil migration to immune stimulus sites, which disrupts the usual immune response.
  • By showing that B cells regulate neutrophil movement and that neutrophils are capturing BCG instead of macrophages, it highlights how this process decreases the activation of IFN-gamma-producing T cells in immune-deficient mice.

Article Abstract

Mutations in the btk gene encoding Bruton's tyrosine kinase cause X-linked immune deficiency, with impaired B lymphocyte function as the major phenotype. Earlier, we demonstrated that CBA/N-xid mice, unlike the wild-type CBA mice, were not protected by bacillus Calmette-Guérin (BCG) vaccination against tuberculosis infection. Because IFN-gamma-producing T cells and activated macrophages are key elements of antituberculosis protection, it remained unclear how the mutation predominantly affecting B cell functions interferes with responses along the T cell-macrophage axis. In this study, we show that B cell deficiency leads to an abnormally rapid neutrophil migration toward the site of external stimulus. Using adoptive cell transfers and B cell genetic knockout, we demonstrate a previously unappreciated capacity of B cells to downregulate neutrophil motility. In our system, an advanced capture of BCG by neutrophils instead of macrophages leads to a significant decrease in numbers of IFN-gamma-producing T cells and impairs BCG performance in X-linked immune-deficient mice. The defect is readily compensated for by the in vivo neutrophil depletion.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917231PMC
http://dx.doi.org/10.4049/jimmunol.0902011DOI Listing

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