Prostaglandin E2 production is enhanced in mice genetically selected to produce high affinity antibody responses

Phillips, Chris

doi:10.1016/0008-8749(89)90252-9

Cited by 4 publications

(4 citation statements)

References 50 publications

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“…Currently, these questions are being evaluated within our laboratory. This study's finding that AID is positively influenced by PGE 2 is consistent with a past report that PGE 2 levels were high in mouse strains characterized by the production of high-affinity Abs (80), and furthermore, that Ab affinity was reduced when antigenic challenge was accompanied by indomethacin (an inhibitor of COX-2 and COX-1) (80). Moreover, these findings may provide an additional mechanism for the augmented switching to IgG and IgE in LPS + IL-4-stimulated mouse B cell cultures supplemented with PGE 2 (10,11,81) and the reduced isotype switching previously noted in immunized COX-2-deficient and mPGES-1-deficient mice (8,9,63).…”

Section: Discussionsupporting

confidence: 92%

A Cyclooxygenase-2/Prostaglandin E2 Pathway Augments Activation-Induced Cytosine Deaminase Expression within Replicating Human B Cells

Lee¹,

Trott²,

Haque³

et al. 2010

The Journal of Immunology

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Within inflammatory environments, B cells encountering foreign or self-Ag can develop tertiary lymphoid tissue expressing activation-induced cytosine deaminase (AID). Recently, this DNA-modifying enzyme was detected in nonlymphoid cells within several inflamed tissues and strongly implicated in malignant transformation. This study examines whether a cyclooxygenase 2 (COX-2) pathway, often linked to inflammation, influences AID expression in activated B lymphocytes. In this paper, we report that dividing human B cells responding to surrogate C3d-coated Ag, IL-4, and BAFF express AID, as well as COX-2. A progressive increase in AID with each division was paralleled by a division-related increase in a COX-2–linked enzyme, microsomal PGE2 synthase-1, and the PGE2R, EP2. Cells with the greatest expression of AID expressed the highest levels of EP2. Although COX-2 inhibitors diminished both AID expression and IgG class switching, exogenous PGE2 and butaprost, a selective EP2 agonist, augmented AID mRNA/protein and increased the numbers of IgG+ progeny. Despite the latter, the proportion of IgG+ cells within viable progeny generally declined with PGE2 supplementation. This was not due to PGE2-promoted differentiation to plasma cells or to greater downstream switching. Rather, because phosphorylated ataxia telangiectasia mutated levels were increased in progeny of PGE2-supplemented cultures, it appears more likely that PGE2 facilitates AID-dependent DNA double-strand breaks that block B cell cycle progression or promote activation-induced cell death, or both. Taken together, the results suggest that a PGE2 feed-forward mechanism for augmenting COX-2 pathway proteins promotes progressively increased levels of AID mRNA, protein, and function.

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Section: Discussionsupporting

confidence: 92%

A Cyclooxygenase-2/Prostaglandin E2 Pathway Augments Activation-Induced Cytosine Deaminase Expression within Replicating Human B Cells

Lee¹,

Trott²,

Haque³

et al. 2010

The Journal of Immunology

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“…49 Indomethacin administered to mice immunized with human serum albumin showed a reduction in antibody affinity and production, and this effect was greater when the drug was given one week before or one week immediately after immunization (p < 0.05 and p < 0.02, respectively), whereas no significant reduction was observed when indomethacin was given during the second week (day 7 to 14). 50 These laboratory data correlate with human studies, such as antibody blunting in the 2009 Prymula study that occurred only in the primary vaccine series "novel antigens" and not when booster vaccines were given, and in the study of Wysocki et al that noted similar results. Additionally, in the 1978 Goodwin study, indomethacin prophylaxis resulted in lower, but not statistically significant, antibody response to the novel influenza A/New Jersey strain but not against the A/Victoria strain that the participants had already been exposed to.…”

Section: Observational Studies Reporting Antipyretic Usesupporting

confidence: 55%

Effect of antipyretic analgesics on immune responses to vaccination

Saleh

Moody

Walter

2016

Human Vaccines & Immunotherapeutics

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While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses.

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“…Type 1 diabetes is an autoimmune disease where a Th1-type immune response is perceived to be important [34,35]. Antibody avidity is also influenced by genetic factors which are associated with a tendency to either high or low avidity antibody responses in a given individual [17]. These genetic factors have not been identified but they may be located in the immunoglobulin gene region.…”

Section: Discussionmentioning

confidence: 99%

“…Maturation of antibody avidity is one of the primary characteristics of B‐cell memory representing the strength with which a multi‐valent antibody is bound to a multi‐valent antigen, and aberrant avidity maturation suggests abnormalities in the regulation of immune responsiveness. Studies using various inbred mouse strains have shown that the maturation of antibody avidity is regulated genetically and may vary between different individuals [17–19]. The cellular immune system, together with cytokines and the Th1/Th2 balance, may play an important role in this regulation and, for example, interferon‐gamma has been shown to augment avidity maturation [20–22].…”

Section: Introductionmentioning

confidence: 99%

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

Heino

Lönnrot

Knip

et al. 2001

Clinical and Experimental Immunology

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SUMMARYEnterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

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Prostaglandin E2 production is enhanced in mice genetically selected to produce high affinity antibody responses

Cited by 4 publications

References 50 publications

A Cyclooxygenase-2/Prostaglandin E2 Pathway Augments Activation-Induced Cytosine Deaminase Expression within Replicating Human B Cells

A Cyclooxygenase-2/Prostaglandin E2 Pathway Augments Activation-Induced Cytosine Deaminase Expression within Replicating Human B Cells

Effect of antipyretic analgesics on immune responses to vaccination

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

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