B cells delay neutrophil migration toward the site of stimulus: tardiness critical for effective bacillus Calmette-Guérin vaccination against tuberculosis infection in mice.
J Immunol
; 184(3): 1227-34, 2010 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-20028653
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tuberculosis, Pulmonary
/
Cell Migration Inhibition
/
BCG Vaccine
/
B-Lymphocyte Subsets
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2010
Type:
Article
Affiliation country:
RUSSIA