B cells delay neutrophil migration toward the site of stimulus: tardiness critical for effective bacillus Calmette-Guérin vaccination against tuberculosis infection in mice.
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.
Kondratieva
Tatiana K
TK
Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia.
Rubakova
Elvira I
EI
Linge
Irina A
IA
Evstifeev
Vladimir V
VV
Majorov
Konstantin B
KB
Apt
Alexander S
AS
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000473:pathology / Q000517:prevention & control*
D001500:BCG Vaccine