{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:16:45Z","timestamp":1789903005817,"version":"4.0.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,12,18]],"date-time":"2009-12-18T00:00:00Z","timestamp":1261094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI078864"],"award-info":[{"award-number":["AI078864"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["07-04-00447"],"award-info":[{"award-number":["07-04-00447"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001744","name":"International Science and Technology Center","doi-asserted-by":"publisher","award":["3626"],"award-info":[{"award-number":["3626"]}],"id":[{"id":"10.13039\/501100001744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in the btk gene encoding Bruton\u2019s 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-Gu\u00e9rin (BCG) vaccination against tuberculosis infection. Because IFN-\u03b3\u2013producing 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\u2013macrophage 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-\u03b3\u2013producing T cells and impairs BCG performance in X-linked immune-deficient mice. The defect is readily compensated for by the in vivo neutrophil depletion.<\/jats:p>","DOI":"10.4049\/jimmunol.0902011","type":"journal-article","created":{"date-parts":[[2009,12,22]],"date-time":"2009-12-22T19:07:50Z","timestamp":1261508870000},"page":"1227-1234","source":"Crossref","is-referenced-by-count":49,"title":["B Cells Delay Neutrophil Migration toward the Site of Stimulus: Tardiness Critical for Effective Bacillus Calmette-Gu\u00e9rin Vaccination against Tuberculosis Infection in Mice"],"prefix":"10.1093","volume":"184","author":[{"given":"Tatiana K","family":"Kondratieva","sequence":"first","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira I","family":"Rubakova","sequence":"additional","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A","family":"Linge","sequence":"additional","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V","family":"Evstifeev","sequence":"additional","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin B","family":"Majorov","sequence":"additional","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S","family":"Apt","sequence":"additional","affiliation":[{"name":"Laboratory for Immunogenetics, Central Institute for Tuberculosis , Moscow,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,18]]},"reference":[{"key":"2026012808090313100_r1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0092-8674(93)90667-F","article-title":"Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.","volume":"72","author":"Tsukada","year":"1993","journal-title":"Cell"},{"key":"2026012808090313100_r2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/361226a0","article-title":"The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.","volume":"361","author":"Vetrie","year":"1993","journal-title":"Nature"},{"key":"2026012808090313100_r3","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1126\/science.8332901","article-title":"Mutation of unique region of Bruton\u2019s tyrosine kinase in immunodeficient XID mice.","volume":"261","author":"Rawlings","year":"1993","journal-title":"Science"},{"key":"2026012808090313100_r4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1126\/science.8332900","article-title":"Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes.","volume":"261","author":"Thomas","year":"1993","journal-title":"Science"},{"key":"2026012808090313100_r5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0065-2776(08)60512-X","article-title":"CD5 B cells, a fetal B cell lineage.","volume":"55","author":"Hardy","year":"1994","journal-title":"Adv. Immunol."},{"key":"2026012808090313100_r6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/1074-7613(95)90114-0","article-title":"Defective B cell development and function in Btk-deficient mice.","volume":"3","author":"Khan","year":"1995","journal-title":"Immunity"},{"key":"2026012808090313100_r7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/1074-7613(95)90115-9","article-title":"Impaired expansion of mouse B cell progenitors lacking Btk.","volume":"3","author":"Kerner","year":"1995","journal-title":"Immunity"},{"key":"2026012808090313100_r8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1084\/jem.184.1.31","article-title":"A role for Bruton\u2019s tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-\u03b3 2.","volume":"184","author":"Takata","year":"1996","journal-title":"J. Exp. Med."},{"key":"2026012808090313100_r9","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1084\/jem.191.10.1745","article-title":"Bruton\u2019s tyrosine kinase is required for activation of I\u03baB kinase and nuclear factor \u03baB in response to B cell receptor engagement.","volume":"191","author":"Petro","year":"2000","journal-title":"J. Exp. Med."},{"key":"2026012808090313100_r10","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1084\/jem.191.10.1735","article-title":"Bruton\u2019s tyrosine kinase links the B cell receptor to nuclear factor \u03baB activation.","volume":"191","author":"Bajpai","year":"2000","journal-title":"J. Exp. Med."},{"key":"2026012808090313100_r11","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1084\/jem.187.8.1235","article-title":"Involvement of Bruton\u2019s tyrosine kinase in Fc\u03b5RI-dependent mast cell degranulation and cytokine production.","volume":"187","author":"Hata","year":"1998","journal-title":"J. Exp. Med."},{"key":"2026012808090313100_r12","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0960-9822(98)70471-3","article-title":"A role for Bruton\u2019s tyrosine kinase (Btk) in platelet activation by collagen.","volume":"8","author":"Quek","year":"1998","journal-title":"Curr. Biol."},{"key":"2026012808090313100_r13","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.4049\/jimmunol.168.6.2914","article-title":"Macrophage effector functions controlled by Bruton\u2019s tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance.","volume":"168","author":"Mukhopadhyay","year":"2002","journal-title":"J. Immunol."},{"key":"2026012808090313100_r14","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1182\/blood-2004-01-0207","article-title":"Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses.","volume":"104","author":"Mangla","year":"2004","journal-title":"Blood"},{"key":"2026012808090313100_r15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1084\/jem.20011140","article-title":"B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen.","volume":"195","author":"Wardemann","year":"2002","journal-title":"J. Exp. Med."},{"key":"2026012808090313100_r16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1365-2249.1996.d01-643.x","article-title":"Influence of the mouse Bcg, Tbc-1 and xid genes on resistance and immune responses to tuberculosis infection and efficacy of bacille Calmette-Gu\u00e9rin (BCG) vaccination.","volume":"104","author":"Nikonenko","year":"1996","journal-title":"Clin. Exp. Immunol."},{"key":"2026012808090313100_r17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev.immunol.19.1.93","article-title":"Immunology of tuberculosis.","volume":"19","author":"Flynn","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2026012808090313100_r18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S1074-7613(00)80189-2","article-title":"Tec kineses: a family with multiple roles in immunity.","volume":"12","author":"Yang","year":"2000","journal-title":"Immunity"},{"key":"2026012808090313100_r19","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/376352a0","article-title":"Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice.","volume":"376","author":"Rickert","year":"1995","journal-title":"Nature"},{"key":"2026012808090313100_r20","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.4049\/jimmunol.165.10.5921","article-title":"Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease.","volume":"165","author":"Lyadova","year":"2000","journal-title":"J. Immunol."},{"key":"2026012808090313100_r21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2249.2004.02328.x","article-title":"Lung cell responses to M. tuberculosis in genetically susceptible and resistant mice following intratracheal challenge.","volume":"135","author":"Eruslanov","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"2026012808090313100_r22","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.tube.2008.05.003","article-title":"A human-like TB in genetically susceptible mice followed by the true dormancy in a Cornell-like model.","volume":"88","author":"Radaeva","year":"2008","journal-title":"Tuberculosis (Edinb.)"},{"key":"2026012808090313100_r23","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-\u0394 \u0394 C(T)) Method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026012808090313100_r24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1365-2567.2008.02950.x","article-title":"Neutrophil mobilization and clearance in the bone marrow.","volume":"125","author":"Furze","year":"2008","journal-title":"Immunology"},{"key":"2026012808090313100_r25","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1182\/blood-2007-07-099648","article-title":"The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation.","volume":"111","author":"Wengner","year":"2008","journal-title":"Blood"},{"key":"2026012808090313100_r26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1165\/rcmb.2002-0038OC","article-title":"Mycobacterium tuberculosis-induced activation accelerates apoptosis in peripheral blood neutrophils from patients with active tuberculosis.","volume":"27","author":"Alem\u00e1n","year":"2002","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026012808090313100_r27","doi-asserted-by":"crossref","first-page":"5150","DOI":"10.1128\/IAI.72.9.5150-5158.2004","article-title":"Mycobacterium tuberculosis triggers apoptosis in peripheral neutrophils involving toll-like receptor 2 and p38 mitogen protein kinase in tuberculosis patients.","volume":"72","author":"Alem\u00e1n","year":"2004","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r28","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1128\/IAI.73.3.1744-1753.2005","article-title":"Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice.","volume":"73","author":"Eruslanov","year":"2005","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r29","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.micinf.2007.11.007","article-title":"Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria.","volume":"10","author":"Persson","year":"2008","journal-title":"Microbes Infect."},{"key":"2026012808090313100_r30","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1182\/blood-2005-03-1281","article-title":"Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes.","volume":"106","author":"Abadie","year":"2005","journal-title":"Blood"},{"key":"2026012808090313100_r31","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/eji.200737905","article-title":"Mycobacterium bovis BCG-infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice.","volume":"38","author":"Morel","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2026012808090313100_r32","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1086\/431680","article-title":"In tuberculous pleural effusions, activated neutrophils undergo apoptosis and acquire a dendritic cell-like phenotype.","volume":"192","author":"Aleman","year":"2005","journal-title":"J. Infect. Dis."},{"key":"2026012808090313100_r33","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1111\/j.1462-5822.2008.01233.x","article-title":"Neutrophils recruited to the site of Mycobacterium bovis BCG infection undergo apoptosis and modulate lipid body biogenesis and prostaglandin E production by macrophages.","volume":"10","author":"D\u2019Avila","year":"2008","journal-title":"Cell. Microbiol."},{"key":"2026012808090313100_r34","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1002\/eji.200636771","article-title":"Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response.","volume":"37","author":"Alem\u00e1n","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2026012808090313100_r35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000071555","article-title":"Phenotypic and functional changes of cytokine-activated neutrophils.","volume":"83","author":"Galligan","year":"2003","journal-title":"Chem. Immunol. Allergy"},{"key":"2026012808090313100_r36","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1159\/000074296","article-title":"CD31 regulates direction and rate of neutrophil migration over and under endothelial cells.","volume":"40","author":"Luu","year":"2003","journal-title":"J. Vasc. Res."},{"key":"2026012808090313100_r37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.imbio.2007.07.001","article-title":"Role of different protein kinases in fMLP-induced neutrophil transmigration.","volume":"213","author":"Zen","year":"2008","journal-title":"Immunobiology"},{"key":"2026012808090313100_r38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4049\/jimmunol.182.1.329","article-title":"Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells.","volume":"182","author":"Sharma","year":"2009","journal-title":"J. Immunol."},{"key":"2026012808090313100_r39","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1128\/iai.63.9.3381-3387.1995","article-title":"Susceptibility of beige mice to Mycobacterium avium: role of neutrophils.","volume":"63","author":"Appelberg","year":"1995","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1128\/IAI.68.2.577-583.2000","article-title":"Neutrophils play a protective nonphagocytic role in systemic Mycobacterium tuberculosis infection of mice.","volume":"68","author":"Pedrosa","year":"2000","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r41","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.1128\/IAI.70.9.5322-5327.2002","article-title":"Neutrophil-mediated mycobacteriocidal immunity in the lung during Mycobacterium bovis BCG infection in C57BL\/6 mice.","volume":"70","author":"Fulton","year":"2002","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r42","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1128\/IAI.00057-06","article-title":"Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes.","volume":"74","author":"Keller","year":"2006","journal-title":"Infect. Immun."},{"key":"2026012808090313100_r43","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1086\/597421","article-title":"Combination of host susceptibility and virulence of Mycobacterium tuberculosis determines dual role of nitric oxide in the protection and control of inflammation.","volume":"199","author":"Beisiegel","year":"2009","journal-title":"J. Infect. Dis."},{"key":"2026012808090313100_r44","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.4049\/jimmunol.173.11.6521","article-title":"Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into macrophages.","volume":"173","author":"van Zandbergen","year":"2004","journal-title":"J. Immunol."},{"key":"2026012808090313100_r45","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1126\/science.1159194","article-title":"In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies.","volume":"321","author":"Peters","year":"2008","journal-title":"Science"},{"key":"2026012808090313100_r46","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1053\/j.gastro.2008.11.035","article-title":"B cells suppress the inflammatory response in a mouse model of primary biliary cirrhosis.","volume":"136","author":"Moritoki","year":"2009","journal-title":"Gastroenterology"},{"key":"2026012808090313100_r47","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.immuni.2008.03.017","article-title":"A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses.","volume":"28","author":"Yanaba","year":"2008","journal-title":"Immunity"},{"key":"2026012808090313100_r48","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.4049\/jimmunol.164.7.3681","article-title":"B cell-deficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology.","volume":"164","author":"Smelt","year":"2000","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/3\/1227\/62719664\/ji_0902011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/3\/1227\/62719664\/ji_0902011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:09:58Z","timestamp":1769605798000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/3\/1227\/8013483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,18]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,12,18]]},"published-print":{"date-parts":[[2010,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0902011","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,2]]},"published":{"date-parts":[[2009,12,18]]}}}