A role for B cells in the development of T cell helper function in a malaria infection in mice

Langhorne, Jean; Cross, Caroline; Seixas, Elsa; Li, Ching; Weid, Thierry von der

doi:10.1073/pnas.95.4.1730

Cited by 152 publications

(150 citation statements)

References 46 publications

(44 reference statements)

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“…Moreover, early in vivo studies showed reduced CD4 cell responses develop when B cells are depleted from normal mice by treatment with anti-IgM Ab (10 -13). More recently, analyses of CD4 responses in B celldeficient mice have in many instances shown diminished CD4-dependent responses to foreign proteins (35,36) and pathogens (37). In our model, we show that a much lower response in B cell-deficient mice is not due to a defect in cytokine production per cell but rather to a markedly reduced level of clonal expansion in response to priming.…”

Section: Discussionmentioning

confidence: 51%

“…In particular, studies of B cell-deficient mice, MT mice that have a targeted deletion of the region (26) or mice in which the J H region (JHD) (34) of the IgM locus is disrupted, suggest both that B cells are completely unnecessary as APC for primary CD4 cell responses, as measured by proliferation and cytokine production to protein (4,5) and viral (9) Ag, and that B cells are necessary as APC for protein (35) but not peptide Ag (36) and for responses to some parasites (37). To assess the requirement of B cells in the development of memory CD4 cells in vivo, we initially compared CD4 responses to KLH in MT mice vs normal C57BL/6 mice over a 3-mo time period.…”

Section: Reduced Cd4 Cell Priming In the Absence Of B Cellsmentioning

confidence: 99%

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A Critical Role for B Cells in the Development of Memory CD4 Cells

Linton

Harbertson

Bradley

2000

The Journal of Immunology

193

148

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Activated B cells express high levels of class II MHC and costimulatory molecules and are nearly as effective as dendritic cells in their APC ability. Yet, their importance as APC in vivo is controversial and their role, if any, in the development of CD4 memory is unknown. We compared responses of CD4 cells from normal and B cell-deficient mice to keyhole limpet hemocyanin over 6 mo and observed diminished IL-2 production by cells primed in the absence of B cells. This was due to lower frequencies of Ag-responsive cells and not to decreased levels of IL-2 secretion per cell. The absence of B cells did not affect the survival of memory CD4 cells since frequencies remained stable. Despite normal dendritic cell function, multiple immunizations of B cell-deficient mice did not restore frequencies of memory cells. However, the transfer of B cells restored memory cell development. Ag presentation was not essential since B cells activated in vitro with irrelevant Ag also restored frequencies of memory cells. The results provide unequivocal evidence that B cells play a critical role in regulating clonal expansion of CD4 cells and, as such, are requisite for the optimal priming of memory in the CD4 population.

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Section: Discussionmentioning

confidence: 51%

Section: Reduced Cd4 Cell Priming In the Absence Of B Cellsmentioning

confidence: 99%

A Critical Role for B Cells in the Development of Memory CD4 Cells

Linton

Harbertson

Bradley

2000

The Journal of Immunology

193

148

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“…They can rapidly take up, catabolize, and present Ags and have been shown to play an important role in optimizing Ag presentation to T cells (44,47). Furthermore, lack of B cells during presentation has been shown to result in reduced T cell responses (44,45,(47)(48)(49). Dendritic cells (DCs) are likely responsible for the limited inflammatory response observed in IgA Ϫ/Ϫ mice; however, the lack of adjuvant during IN challenge in this model would cause suboptimal DC activation and maturation.…”

Section: Discussionmentioning

confidence: 99%

Mucosal B Cell Deficiency in IgA−/− Mice Abrogates the Development of Allergic Lung Inflammation

Arnaboldi

Behr

Metzger

2005

The Journal of Immunology

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We have investigated the consequence of lack of IgA on host immunity using a murine model of allergic lung inflammation. Mice with a targeted disruption of the α-switch region and 5′ H chain gene (IgA−/− mice), which lack total IgA, developed significantly reduced pulmonary inflammation with fewer inflammatory cells in lung tissue and bronchoalveolar lavage fluids, as well as reduced levels of total and IgG1 OVA-specific Abs and decreased IL-4 and IL-5 in bronchoalveolar lavage fluids compared with IgA+/+ controls, following allergen sensitization and challenge. This defect was attributable to fewer B cells in the lungs of IgA−/− mice. Polymeric IgR-deficient (pIgR−/−) mice, which lack the receptor that transports polymeric IgA across the mucosal epithelium where it is cleaved to form secretory IgA, were used to assess the contribution of secretory IgA vs total IgA in the induction of allergic lung inflammation. pIgR−/− and pIgR+/+ mice had comparable levels of inflammation, demonstrating that IgA bound to secretory component is not necessary for the development of allergic lung inflammation, although this does not necessarily rule out a role for transudated IgA in lung secretions because of “mucosal leakiness” in these mice. The results indicate that Ag-specific B cells are required at mucosal surfaces for induction of inflammation and likely function as major APCs in the lung for soluble protein Ags.

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“…The underlying mechanisms are not known, but B cells play a developmental role in the formation of the intestinal lymphoid tissue (7), which may be important for the detection of bacterial pathogens and for mounting effective immune defenses, even in the absence of a direct B-cell involvement. B cells are also potent antigen-presenting cells (9,30) and have been shown to facilitate the development of effective T-cell responses in host defense against microbial infections (19,42). In addition, B cells can secrete chemotactic cytokines that are important for the recruitment of immune and inflammatory cells (17).…”

Section: Discussionmentioning

confidence: 99%

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

et al. 2004

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Citrobacter rodentium, a murine model pathogen for human enteropathogenic Escherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected with C. rodentium develop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oral C. rodentium infections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense against C. rodentium depends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.

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A role for B cells in the development of T cell helper function in a malaria infection in mice

Cited by 152 publications

References 46 publications

A Critical Role for B Cells in the Development of Memory CD4 Cells

A Critical Role for B Cells in the Development of Memory CD4 Cells

Mucosal B Cell Deficiency in IgA−/− Mice Abrogates the Development of Allergic Lung Inflammation

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

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