IL-7–Dependent B Lymphocytes Are Essential for the Anti-polysaccharide Response and Protective Immunity to<i>Streptococcus</i> <i>pneumoniae</i>

Shriner, Anne K.; Liu, Hongqi; Sun, Guizhi; Guimond, Martin; Alugupalli, Kishore R.

doi:10.4049/jimmunol.0902841

Cited by 31 publications

(60 citation statements)

References 71 publications

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“…Since B1b cells are the primary responders to the prototypical TI-2 antigen NP-Ficoll, as well as to B. hermsii (2,4,36,40), we analyzed the B1b cell compartments of TACI Ϫ/Ϫ , BAFFR Ϫ/Ϫ , and BAFF Ϫ/Ϫ mice. We found that TACI-, BAFFR-, and BAFF-deficient mice all possessed a comparable frequency of B1b cells, though BAFFR-and BAFFdeficient mice possessed significantly fewer B1 cells than did wildtype or TACI-deficient mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For NP-Ficoll immunization, 50 g of 77-NP-loaded-Ficoll (Biosearch Technologies, Petaluma, CA) dissolved in 100 l Dulbecco's phosphate-buffered saline was used to immunize mice intraperitoneally (36). For pneumococcal immunizations, mice were injected intraperitoneally with 1 ϫ 10 8 encapsulated, heat-killed cells of the WU-2 strain of S. pneumoniae (36).…”

Section: Methodsmentioning

confidence: 99%

“…The level of B. hermsii-, FhbA-, NP-, or type 3 pneumococcal polysaccharide (PPS3)-specific IgM or IgG was determined as described previously (3,20,21,36) Specific antibody levels were interpreted as ng/l equivalents using enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions (Bethyl Laboratories, Montgomery, TX).…”

Section: Methodsmentioning

confidence: 99%

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Efficient B Cell Responses to Borrelia hermsii Infection Depend on BAFF and BAFFR but Not TACI

et al. 2014

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bT cell-independent antibody responses develop rapidly, within 3 to 4 days, and are critical for preventing blood-borne pathogens from evolving into life-threatening infections. The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and function. Using a synthetic polysaccharide antigen, it has previously been shown that TACI is critical for T cell-independent antibody responses. To examine the role of BAFFR and TACI in T cell-independent antibody responses to an active infection, we utilized the Borrelia hermsii infection system. In this infection system, T cell-independent responses mediated by the B1b cell subset are critical for controlling bacteremia. We found that B1b cells express BAFFR and TACI and that the surface expression of both receptors is upregulated on B1b cells following exposure to whole B. hermsii cells. Surprisingly, we found that TACI ؊/؊ mice are not impaired either in specific antibody responses to B. hermsii or in controlling B. hermsii bacteremia. In contrast, TACI-deficient mice immunized with heat-killed type 3 serotype pneumococcus cells are impaired in generating pneumococcal polysaccharide-specific responses and succumb to challenge with live type 3 serotype pneumococcus, indicating that TACI is required for T cell-independent antibody responses to bacterial-associated polysaccharides. Although we have found that TACI is dispensable for controlling B. hermsii infection, mice deficient in BAFFR or BAFF exhibit impairment in B. hermsii-specific IgM responses and clearance of bacteremia. Collectively, these data indicate a disparity in the roles for TACI and BAFFR in primary T cell-independent antibody responses to bacterial pathogens.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Efficient B Cell Responses to Borrelia hermsii Infection Depend on BAFF and BAFFR but Not TACI

et al. 2014

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“…Although its effect on B-cell development in HISmice has not been characterized, administration of human IL-7 might augment B-cell development quantitatively and qualitatively (39)(40)(41). For example, IL-7 was shown to increase B-cell receptor (BCR) diversity in mice (40), and IL-7-dependent murine B cells play an important role in generating a T cell-independent responses to a variety of antigens (42).…”

Section: Discussionmentioning

confidence: 99%

Characteristics ofBorrelia hermsiiinfection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever

Vuyyuru

Liu

Manser

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fever (RF) in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans. We examined Borrelia hermsii infection in human hematopoietic stem cell-engrafted nonobese diabetic/SCID/IL-2Rγ null mice: “human immune system mice” (HISmice). Infection of these mice, which are severely deficient in lymphoid and myeloid compartments, with B. hermsii resulted in persistent bacteremia. In contrast, this infection in HISmice resulted in recurrent episodes of bacteremia, the hallmark of RF. The resolution of the primary episode of bacteremia was concurrent with the generation of B. hermsii -specific human IgM. Remarkably, HISmice generated antibody responses to the B. hermsii outer-membrane protein Factor H binding protein A. Sera from humans infected by B. hermsii have a similar reactivity, and studies in mice have shown that this response is generated by the B1b cell subset. HISmice contain several B-cell subsets, including those with the phenotype CD20 + CD27 + CD43 + CD70 − , a proposed human equivalent of mouse B1 cells. Reduction of B cells by administration of anti-human CD20 antibody resulted in diminished anti- B. hermsii responses and persistent bacteremia in HISmice. These data indicate that analysis of B. hermsii infection in HISmice will serve as a model in which to study the cellular and molecular mechanisms involved in controlling human RF.

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“…5). A possible explanation for the comparable NP-specific IgM responses between wild-type and Cxcl13 Ϫ/Ϫ mice after NP-Ficoll immunization could be the participation of other B cell subsets (45) or B1b cells outside the peritoneal cavity. Indeed, we found that Cxcl13 Ϫ/Ϫ mice had a higher frequency of Mac1-negative NP-specific B cells in the blood, MLNs, and spleen than did wild-type mice (Table 1).…”

Section: Mice Np-ficoll Is a Widely Used Model Antigen For Studying mentioning

confidence: 99%

T-Cell-Independent Immune Responses Do Not Require Cxc Ligand 13-Mediated B1 Cell Migration

2010

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The dynamic movement of B cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. B1a and B1b cells are enriched in the coelomic cavity, contribute to T-cell-independent (TI) antibody responses, and increase in number upon antigen exposure. B1 cell movement is largely governed by Cxc ligand 13 (Cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal B1 cells. In this study, we examined the role of Cxcl13-dependent B cell migration using Borrelia hermsii infection or intraperitoneal immunization with pneumococcal polysaccharide or 4-hydroxy-3-nitrophenyl-acetyl (NP)-Ficoll, all of which induce robust antibody responses from B1b cells. Surprisingly, we found that antibody responses to B. hermsii or to FhbA, an antigenic target of B1b cells, and the resolution of bacteremia were indistinguishable between wild-type and Cxcl13 ؊/؊ mice. Importantly, we did not observe an expansion of peritoneal B1b cell numbers in Cxcl13 ؊/؊ mice. Nonetheless, mice that had resolved infection were resistant to reinfection, indicating that the peritoneal B1b cell reservoir is not required for controlling B. hermsii. Furthermore, despite a reduced peritoneal B1b compartment, immunization with pneumococcal polysaccharide vaccine yielded comparable antigen-specific antibody responses in wild-type and Cxcl13 ؊/؊ mice and conferred protection against Streptococcus pneumoniae. Likewise, immunization with NP-Ficoll elicited similar antibody responses in wild-type and Cxcl13؊/؊ mice. These data demonstrate that homing of B1 cells into the coelomic cavity is not a requirement for generating protective TI antibody responses, even when antigen is initially localized to this anatomical compartment.

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IL-7–Dependent B Lymphocytes Are Essential for the Anti-polysaccharide Response and Protective Immunity toStreptococcus pneumoniae

Abstract: Material

Cited by 31 publications

References 71 publications

Efficient B Cell Responses to Borrelia hermsii Infection Depend on BAFF and BAFFR but Not TACI

Efficient B Cell Responses to Borrelia hermsii Infection Depend on BAFF and BAFFR but Not TACI

Characteristics ofBorrelia hermsiiinfection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever

T-Cell-Independent Immune Responses Do Not Require Cxc Ligand 13-Mediated B1 Cell Migration

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