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

Colombo, Matthew J.; Sun, Guizhi; Alugupalli, Kishore R.

doi:10.1128/iai.00371-10

Cited by 10 publications

(13 citation statements)

References 49 publications

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“…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%

“…Although immunocompetent mice suffer multiple episodes of bacteremia, the severity of bacteremia typically decreases in each subsequent episode, and by 4 weeks, the bacteremia is undetectable (3,(15)(16)(17). In mice, the decrease in the severity of bacteremic episodes correlates to the gradual generation of TI IgM responses specific to factor H-binding protein (FhbA) (20,21), an outer membrane protein and putative virulence factor that is constitutively expressed by B. hermsii (22,23), suggesting that the gradual generation of IgM specific for this conserved antigenic target may be responsible for the eventual resolution of infection. Using the B. hermsii infection system, we have defined a major role for B1b cells in TI immune responses (2,3,16,20).…”

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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: Methodsmentioning

confidence: 99%

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confidence: 99%

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

et al. 2014

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“…While the majority of published findings on the induction of α‐PEG are consistent with this TI‐2 mechanism, there are a small number of studies that present contrasting results. TI responses typically do not induce significant memory or antibody class switching unless there is strong co‐stimulation by noncognate immune cells and/or secreted factors such as cytokines (e.g., IL‐1, IL‐6, TNFα) . While IgM is indeed the dominant α‐PEG Ab isotype observed, a few studies have reported anti‐PEG IgG responses .…”

Section: Peg‐specific Immunity In Animal Modelsmentioning

confidence: 99%

Anti‐PEG immunity: emergence, characteristics, and unaddressed questions

Yang

Lai

2015

WIREs Nanomed Nanobiotechnol

483

433

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The modification of protein and nanoparticle therapeutics with polyethylene glycol (PEG), a flexible, uncharged and highly hydrophilic polymer, is a widely adopted approach to reduce RES clearance, extend circulation time, and improve drug efficacy. Nevertheless, an emerging body of literature, generated by numerous research groups, demonstrates that the immune system can produce antibodies that specifically bind PEG, which can lead to the “accelerated blood clearance” of PEGylated therapeutics. In animals, anti-PEG immunity is typically robust but short-lived and consists of a predominantly anti-PEG IgM response. Rodent studies suggest that the induction of anti-PEG antibodies (α-PEG Abs) primarily occurs through a type 2 T-cell independent mechanism. Although anti-PEG immunity is less well-studied in humans, the presence of α-PEG Abs has been correlated with reduced efficacy of PEGylated therapeutics in clinical trials. The prevalence of anti-PEG IgG and reports of memory immune responses, as well as the existence of α-PEG Abs in healthy untreated individuals, suggests that the mechanism(s) and features of human anti-PEG immune responses may differ from those of animal models. Many questions, including the incidence rate of pre-existing α-PEG Abs and immunological mechanism(s) of α-PEG Ab formation in humans, must be answered in order to fully address the potential complications of anti-PEG immunity.

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“…They are most associated with some serosal sites such as the peritoneal cavity, although they can also be detected in secondary lymphoid tissues and so are probably more widespread than currently appreciated (78, 79). A key feature that distinguishes B1 subsets from B2 subsets is their capacity to self-renew.…”

Section: The Distinct Flavors Of B-cell Subsetsmentioning

confidence: 99%

B1b Cells Recognize Protective Antigens after Natural Infection and Vaccination

Cunningham¹,

Flores‐Langarica²,

Bobat³

et al. 2014

Front. Immunol.

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There are multiple, distinct B-cell populations in human beings and other animals such as mice. In the latter species, there is a well-characterized subset of B-cells known as B1 cells, which are enriched in peripheral sites such as the peritoneal cavity but are rare in the blood. B1 cells can be further subdivided into B1a and B1b subsets. There may be additional B1 subsets, though it is unclear if these are distinct populations or stages in the developmental process to become mature B1a and B1b cells. A limitation in understanding B1 subsets is the relative paucity of specific surface markers. In contrast to mice, the existence of B1 cells in human beings is controversial and more studies are needed to investigate the nature of these enigmatic cells. Examples of B1b antigens include pneumococcal polysaccharide and the Vi antigen from Salmonella Typhi, both used routinely as vaccines in human beings and experimental antigens such as haptenated-Ficoll. In addition to inducing classical T-dependent responses some proteins are B1b antigens and can induce T-independent (TI) immunity, examples include factor H binding protein from Borrelia hermsii and porins from Salmonella. Therefore, B1b antigens can be proteinaceous or non-proteinaceous, induce TI responses, memory, and immunity, they exist in a diverse range of pathogenic bacteria, and a single species can contain multiple B1b antigens. An unexpected benefit to studying B1b cells is that they appear to have a propensity to recognize protective antigens in bacteria. This suggests that studying B1b cells may be rewarding for vaccine design as immunoprophylactic and immunotherapeutic interventions become more important due to the decreasing efficacy of small molecule antimicrobials.

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

Cited by 10 publications

References 49 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

Anti‐PEG immunity: emergence, characteristics, and unaddressed questions

B1b Cells Recognize Protective Antigens after Natural Infection and Vaccination

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