B Cells Delay Neutrophil Migration toward the Site of Stimulus: Tardiness Critical for Effective Bacillus Calmette-Guerin Vaccination against Tuberculosis Infection in Mice

• Published in: The Journal of immunology (1950) Vol. 184; no. 3; pp. 1227 - 1234
• Main Authors: Kondratieva, Tatiana K, Rubakova, Elvira I, Linge, Irina A, Evstifeev, Vladimir V, Majorov, Konstantin B, Apt, Alexander S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2010
• Subjects: Adoptive Transfer; Animals; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - transplantation; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; Cell Line; Cell Migration Inhibition - immunology; Chemotaxis, Leukocyte - genetics; Chemotaxis, Leukocyte - immunology; Female; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Time Factors; Tuberculosis, Pulmonary - pathology; Tuberculosis, Pulmonary - prevention & control
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902011

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.