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Consequentially, animals lacking btk have few B1a cells, minimal Ab responses, and can preferentially generate Th1-type immune responses following infection. B1a cells have been shown to aid in protection against infection with attenuated Francisella tularensis, but their role in infection mediated by fully virulent F. tularensis is not known. Therefore, we used mice with defective btk (CBA\/CaHN-BtkXID\/J [XID mice]) to determine the contribution of B1a cells in defense against the virulent F. tularensis ssp. tularensis strain SchuS4. Surprisingly, XID mice displayed increased resistance to pulmonary infection with F. tularensis. Specifically, XID mice had enhanced clearance of bacteria from the lung and spleen and significantly greater survival of infection compared with wild-type controls. We revealed that resistance to infection in XID mice was associated with decreased numbers of IL-10\u2013producing B1a cells and concomitant increased numbers of IL-12\u2013producing macrophages and IFN-\u03b3\u2013producing NK\/NKT cells. Adoptive transfer of wild-type B1a cells into XID mice reversed the control of bacterial replication. Similarly, depletion of NK\/NKT cells also increased bacterial burdens in XID mice. Together, our data suggest B cell\u2013NK\/NKT cell cross-talk is a critical pivot controlling survival of infection with virulent F. tularensis.<\/jats:p>","DOI":"10.4049\/jimmunol.1202697","type":"journal-article","created":{"date-parts":[[2013,2,2]],"date-time":"2013-02-02T02:58:25Z","timestamp":1359773905000},"page":"2756-2766","source":"Crossref","is-referenced-by-count":33,"title":["B1a Cells Enhance Susceptibility to Infection with Virulent <i>Francisella tularensis<\/i> via Modulation of NK\/NKT Cell Responses"],"prefix":"10.1093","volume":"190","author":[{"given":"Deborah D","family":"Crane","sequence":"first","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases\/National Institutes of Health , Hamilton, MT 59840"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda J","family":"Griffin","sequence":"additional","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases\/National Institutes of Health , Hamilton, MT 59840"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara D","family":"Wehrly","sequence":"additional","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases\/National Institutes of Health , Hamilton, MT 59840"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharine M","family":"Bosio","sequence":"additional","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases\/National Institutes of Health , Hamilton, MT 59840"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"2025032406431933000_r1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12026-012-8372-9","article-title":"Division of labor during primary humoral immunity","volume":"55","author":"Swanson","year":"2013","journal-title":"Immunol. 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