{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:26:33Z","timestamp":1790270793153,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T cell-independent Abs are protective against Lyme disease and relapsing fever, illnesses caused by Borrelia spirochetes with distinct blood-borne phases of infection. To understand this protective response, we characterized splenic and peritoneal B cell compartments during infection using flow cytometry and immunohistochemistry. In the spleen, early after infection, Borrelia crocidurae, a relapsing fever species, induced a striking loss of marginal zone (MZ) B cells from the MZ, while Borrelia burgdorferi, the agent of Lyme disease, induced the expansion of this subset. At the same time, no significant changes were observed in follicular B cells in response to either species of Borrelia. In the peritoneal cavity, a further loss was demonstrated early in response to B. crocidurae in the B1b, B1c, and B2 cell subsets, but B1a cells were not significantly altered. The loss of B1c and B2 cells was sustained through subsequent peaks of spirochetemia, suggesting these subsets may be important in resolving relapsing episodes. In contrast, an early and significant increase in peritoneal B1a, B1b, and B1c cells, but not B2 cells, occurred in response to B. burgdorferi. Later in the course of infection, both species of Borrelia induced the selective expansion of peritoneal B1b cells, suggesting that B1b cells may participate in long-lasting immunity to Lyme and relapsing fever spirochetes. Our data demonstrate that different Borrelia can activate the same B cell subsets in distinct ways and they each elicit a complex interplay of MZ and multiple peritoneal B cell subsets in the early response to infection.<\/jats:p>","DOI":"10.4049\/jimmunol.182.1.498","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:17:12Z","timestamp":1397863032000},"page":"498-506","source":"Crossref","is-referenced-by-count":23,"title":["The Loss and Gain of Marginal Zone and Peritoneal B Cells Is Different in Response to Relapsing Fever and Lyme Disease <i>Borrelia<\/i>"],"prefix":"10.1093","volume":"182","author":[{"given":"Susan","family":"Malkiel","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases, Department of Molecular Genetics and Microbiology, Stony Brook University , Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Kuhlow","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases, Department of Molecular Genetics and Microbiology, Stony Brook University , Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Mena","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases, Department of Molecular Genetics and Microbiology, Stony Brook University , Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L","family":"Benach","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases, Department of Molecular Genetics and Microbiology, Stony Brook University , Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,1,1]]},"reference":[{"key":"2025032622114517300_R1","first-page":"63","article-title":"The important and diverse roles of antibodies in the host response to Borrelia infections.","volume-title":"Curr. Top. Microbiol. Immunol.","year":"2008"},{"key":"2025032622114517300_R2","first-page":"411","article-title":"The versatile roles of antibodies in Borrelia infections.","volume-title":"Nat. Rev. Microbiol.","year":"2005"},{"key":"2025032622114517300_R3","first-page":"751","article-title":"Brief communication: hematogenous dissemination in early Lyme disease.","volume-title":"Ann. Intern. Med.","year":"2005"},{"key":"2025032622114517300_R4","first-page":"155","article-title":"Antigenic variation of a relapsing fever Borrelia species.","volume-title":"Annu. Rev. Microbiol.","year":"1990"},{"key":"2025032622114517300_R5","first-page":"4858","article-title":"Complement factor H-binding protein, a putative virulence determinant of Borrelia hermsii, is an antigenic target for protective B1b lymphocytes.","volume-title":"J. Immunol.","year":"2008"},{"key":"2025032622114517300_R6","first-page":"415","article-title":"An immune evasion mechanism for spirochetal persistence in Lyme borreliosis.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2025032622114517300_R7","first-page":"275","article-title":"Molecular adaptation of Borrelia burgdorferi in the murine host.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2025032622114517300_R8","first-page":"5759","article-title":"Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses.","volume-title":"Infect. Immun.","year":"2004"},{"key":"2025032622114517300_R9","first-page":"5177","article-title":"Constitutive expression of outer surface protein C diminishes the ability of Borrelia burgdorferi to evade specific humoral immunity.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2025032622114517300_R10","first-page":"275","article-title":"Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes.","volume-title":"Cell","year":"1997"},{"key":"2025032622114517300_R11","first-page":"1319","article-title":"Mutation and recombination in the upstream homology box-flanked ospE-related genes of the Lyme disease spirochetes result in the development of new antigenic variants during infection.","volume-title":"Infect. Immun.","year":"2000"},{"key":"2025032622114517300_R12","first-page":"1526","article-title":"Molecular and evolutionary analysis of Borrelia burgdorferi 297 circular plasmid-encoded lipoproteins with OspE- and OspF-like leader peptides.","volume-title":"Infect. Immun.","year":"1999"},{"key":"2025032622114517300_R13","first-page":"1319","article-title":"Antigenic variation with a twist\u2013the Borrelia story.","volume-title":"Mol. Microbiol.","year":"2006"},{"key":"2025032622114517300_R14","first-page":"3698","article-title":"Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion.","volume-title":"Infect. Immun.","year":"1998"},{"key":"2025032622114517300_R15","first-page":"3689","article-title":"Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi.","volume-title":"Infect. Immun.","year":"1998"},{"key":"2025032622114517300_R16","first-page":"5190","article-title":"T-cell-independent responses to Borrelia burgdorferi are critical for protective immunity and resolution of Lyme disease.","volume-title":"Infect. Immun.","year":"2000"},{"key":"2025032622114517300_R17","first-page":"5682","article-title":"Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells.","volume-title":"J. Immunol.","year":"1997"},{"key":"2025032622114517300_R18","first-page":"1","article-title":"Protective antibodies in murine Lyme disease arise independently of CD40 ligand.","volume-title":"J. Immunol.","year":"1996"},{"key":"2025032622114517300_R19","first-page":"3819","article-title":"The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes.","volume-title":"J. Immunol.","year":"2003"},{"key":"2025032622114517300_R20","first-page":"379","article-title":"B1b lymphocytes confer T cell-independent long-lasting immunity.","volume-title":"Immunity","year":"2004"},{"key":"2025032622114517300_R21","first-page":"572","article-title":"T-cell-independent elimination of Borrelia turicatae.","volume-title":"Infect. Immun.","year":"1984"},{"key":"2025032622114517300_R22","first-page":"229","article-title":"Characterization of protective antibodies produced in mice infected with Borrelia duttonii.","volume-title":"Jpn. J. Med. Sci. Biol.","year":"1973"},{"key":"2025032622114517300_R23","first-page":"1009","article-title":"In vitro and in vivo neutralization of the relapsing fever agent Borrelia hermsii with serotype-specific immunoglobulin M antibodies.","volume-title":"Infect. Immun.","year":"2001"},{"key":"2025032622114517300_R24","first-page":"3029","article-title":"Cutting edge: the spirochetemia of murine relapsing fever is cleared by complement-independent bactericidal antibodies.","volume-title":"J. Immunol.","year":"2001"},{"key":"2025032622114517300_R25","first-page":"675","article-title":"Protective activity of Borrelia duttonii-specific immunoglobulin subclasses in mice.","volume-title":"J. Med. Microbiol.","year":"1997"},{"key":"2025032622114517300_R26","first-page":"1191","article-title":"Generation of a complement-independent bactericidal IgM against a relapsing fever Borrelia.","volume-title":"J. Immunol.","year":"2004"},{"key":"2025032622114517300_R27","first-page":"465","article-title":"In vivo evidence that an intact lytic complement pathway is not essential for successful removal of circulating Borrelia turicatae from mouse blood.","volume-title":"Infect. Immun.","year":"1981"},{"key":"2025032622114517300_R28","first-page":"6222","article-title":"Bactericidal action of a complement-independent antibody against relapsing fever Borrelia resides in its variable region.","volume-title":"J. Immunol.","year":"2008"},{"key":"2025032622114517300_R29","first-page":"4523","article-title":"The 39-kilodalton protein of Borrelia burgdorferi: a target for bactericidal human monoclonal antibodies.","volume-title":"Infect. Immun.","year":"1993"},{"key":"2025032622114517300_R30","first-page":"165","article-title":"In vitro inhibition of Borrelia burgdorferi growth by antibodies.","volume-title":"J. Infect. Dis.","year":"1993"},{"key":"2025032622114517300_R31","first-page":"2037","article-title":"A bactericidal antibody to Borrelia burgdorferi is directed against a variable region of the OspB protein.","volume-title":"Infect. Immun.","year":"1994"},{"key":"2025032622114517300_R32","first-page":"2221","article-title":"Molecular analysis of neutralizing epitopes on outer surface proteins A and B of Borrelia burgdorferi.","volume-title":"Infect. Immun.","year":"1995"},{"key":"2025032622114517300_R33","first-page":"3098","article-title":"Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB.","volume-title":"Infect. Immun.","year":"1992"},{"key":"2025032622114517300_R34","first-page":"1908","article-title":"Characterization of the physiological requirements for the bactericidal effects of a monoclonal antibody to OspB of Borrelia burgdorferi by confocal microscopy.","volume-title":"Infect. 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Lett.","year":"2006"},{"key":"2025032622114517300_R47","first-page":"5195","article-title":"CD11b expression distinguishes sequential stages of peritoneal B-1 development.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2008"},{"key":"2025032622114517300_R48","first-page":"364","article-title":"Control of B-cell responses by Toll-like receptors.","volume-title":"Nature","year":"2005"},{"key":"2025032622114517300_R49","first-page":"810","article-title":"Toll-like receptor stimulation as a third signal required for activation of human naive B cells.","volume-title":"Eur. J. Immunol.","year":"2006"},{"key":"2025032622114517300_R50","first-page":"1114","article-title":"Peritoneal B-2 cells comprise a distinct B-2 cell population with B-1b-like characteristics.","volume-title":"Eur. J. Immunol.","year":"2006"},{"key":"2025032622114517300_R51","first-page":"987","article-title":"Rapid and sensitive quantification of Borrelia burgdorferi-infected mouse tissues by continuous fluorescent monitoring of PCR.","volume-title":"J. Clin. Microbiol.","year":"1999"},{"key":"2025032622114517300_R52","first-page":"2366","article-title":"Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses.","volume-title":"Eur. J. Immunol.","year":"1997"},{"key":"2025032622114517300_R53","first-page":"1333","article-title":"Mouse macrophage hemagglutinin (sheep erythrocyte receptor) with specificity for sialylated glycoconjugates characterized by a monoclonal antibody.","volume-title":"J. Exp. Med.","year":"1989"},{"key":"2025032622114517300_R54","first-page":"3264","article-title":"Coligation of the B cell receptor with complement receptor type 2 (CR2\/CD21) using its natural ligand C3dg: activation without engagement of an inhibitory signaling pathway.","volume-title":"J. Immunol.","year":"2005"},{"key":"2025032622114517300_R55","first-page":"133","article-title":"Lyme borreliosis in selected strains and ages of laboratory mice.","volume-title":"J. Infect. Dis.","year":"1990"},{"key":"2025032622114517300_R56","first-page":"323","article-title":"Marginal-zone B cells.","volume-title":"Nat. Rev. Immunol.","year":"2002"},{"key":"2025032622114517300_R57","first-page":"e863","article-title":"Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets.","volume-title":"PLoS ONE","year":"2007"},{"key":"2025032622114517300_R58","first-page":"7779","article-title":"TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses.","volume-title":"J. Immunol.","year":"2007"},{"key":"2025032622114517300_R59","first-page":"3882","article-title":"TLR agonists promote marginal zone B cell activation and facilitate T-dependent IgM responses.","volume-title":"J. Immunol.","year":"2008"},{"key":"2025032622114517300_R60","first-page":"3740","article-title":"MyD88- and Bruton\u2019s tyrosine kinase-mediated signals are essential for T cell-independent pathogen-specific IgM responses.","volume-title":"J. 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Microbiol. Immunol.","year":"2008"},{"key":"2025032622114517300_R70","first-page":"4627","article-title":"The peritoneal micromilieu commits B cells to home to body cavities and the small intestine.","volume-title":"Blood","year":"2007"},{"key":"2025032622114517300_R71","first-page":"6456","article-title":"Natural antibody affects survival of the spirochete Borrelia burgdorferi within feeding ticks.","volume-title":"Infect. Immun.","year":"2001"},{"key":"2025032622114517300_R72","first-page":"780","article-title":"Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10\u201320 years after active Lyme disease.","volume-title":"Clin. Infect. Dis.","year":"2001"},{"key":"2025032622114517300_R73","first-page":"625","article-title":"Cellular immune findings in Lyme disease: correlation with serum IgM and disease activity.","volume-title":"Am. J. Med.","year":"1984"},{"key":"2025032622114517300_R74","first-page":"648","article-title":"In vivo and in vitro evidence of B cell hyperactivity during Lyme disease.","volume-title":"J. Rheumatol.","year":"1988"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/1\/498\/62682705\/8342.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/1\/498\/62682705\/8342.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T20:20:44Z","timestamp":1743279644000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/1\/498\/8004475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1,1]]},"references-count":74,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.182.1.498","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,1]]},"published":{"date-parts":[[2009,1,1]]}}}