Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players

Nicolai, Oliver; Pötschke, Christian; Schmoeckel, Katrin; Darisipudi, Murthy N.; Linde, Julia van der; Raafat, Dina; Bröker, Barbara M.

doi:10.3389/fimmu.2020.00828

Cited by 6 publications

(12 citation statements)

References 98 publications

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“…We and others have shown that sepsis induced a marked increase in serum IgM levels followed by an even stronger IgG response (11,13). As we have previously shown, most ASCs reside in the spleen, and the class switch to IgG results from both TI and TD processes (14). Since the antigen-specific T cell response is still fully functional at the onset of sepsis (47), we assumed that the class switched IgG response was mainly directed at the invasive bacteria.…”

Section: A Strong Induction Of Total Serum Igg During Sepsis Was Not mentioning

confidence: 97%

“…In fact, Mohr et al have shown that B cell priming with defined antigens is defective in sepsis (13). By contrast, we and other research groups have shown that sepsis induces high concentrations of serum IgM and IgG antibodies of unknown specificities (13,14). Since these may be responsible for the observed antibodymediated protection, we set out to examine their antigen specificities in a mouse model of abdominal sepsis.…”

Section: Introductionmentioning

confidence: 93%

“…To study the sepsis-induced antibodies at a single-cell level, monoclonal antibodies (mAbs) were generated. Since we discovered the spleen as the main source of antibody secreting cells (ASCs) in sepsis (14), splenocytes from eight septic mice were obtained on day 10 after sepsis induction and fused. Three quarters (74.3%) of the hybridomas from septic mice produced IgM ( Table 2).…”

Section: Studies At the Single Cell Level Revealed A High Proportion mentioning

confidence: 99%

“…Three quarters (74.3%) of the hybridomas from septic mice produced IgM ( Table 2). However, sepsis induced a much stronger increase in serum IgG than IgM, which peaked at day 14 (14). Assuming that the class switch to IgG may not have been completed on day 10 after sepsis induction, additional fusions were performed using splenocytes from six septic mice on day 14.…”

Section: Studies At the Single Cell Level Revealed A High Proportion mentioning

confidence: 99%

“…Very early in the course of an infection, they differentiate to IgM-or IgG-secreting cells (38). Both TD as well as TI processes take place during sepsis, and all B cell populations become activated (8,14). We have therefore tested sepsis-induced IgM-and IgG-binding to a broad panel of bacterial as well as autoantigens.…”

Section: Introductionmentioning

confidence: 99%

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Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

et al. 2020

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In murine abdominal sepsis by colon ascendens stent peritonitis (CASP), a strong increase in serum IgM and IgG antibodies was observed, which reached maximum values 14 days following sepsis induction. The specificity of this antibody response was studied in serum and at the single cell level using a broad panel of bacterial, sepsis-unrelated as well as self-antigens. Whereas an antibacterial IgM/IgG response was rarely observed, studies at the single-cell level revealed that IgM antibodies, in particular, were largely polyreactive. Interestingly, at least 16% of the IgM mAbs and 20% of the IgG mAbs derived from post-septic mice showed specificity for oxidation-specific epitopes (OSEs), which are known targets of the innate/adaptive immune response. This identifies those self-antigens as the main target of B cell responses in sepsis.

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Section: A Strong Induction Of Total Serum Igg During Sepsis Was Not mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 93%

Section: Studies At the Single Cell Level Revealed A High Proportion mentioning

confidence: 99%

Section: Studies At the Single Cell Level Revealed A High Proportion mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

et al. 2020

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The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice

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Kopparapu

et al. 2023

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Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/− mice, whereas IgG response was impaired in both aged and TLR2−/− mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/− mice. Both aging and TLR2−/− increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/− mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.

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S1PR4 deficiency results in reduced germinal center formation but only marginally affects antibody production

et al. 2022

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IntroductionSplenic B cells exhibit a high expression of the G protein-coupled sphingosine-1-phosphate (S1P) receptor type 4 (S1PR4). Little is known about the functional relevance of S1PR4 expression on those cells.MethodsIn this study, S1PR4-deficient mice were used to study the role of S1PR4-mediated S1P signaling in B cell motility in vitro and for the maintenance of the splenic architecture under steady state conditions as well as in polymicrobial abdominal sepsis in vivo. Finally, the impact of S1PR4 deficiency on antibody production after immunization with T cell dependent antigens was assessed.ResultsLoss of S1PR4 resulted in minor alterations of the splenic architecture concerning the presence of B cell follicles. After sepsis induction, the germinal center response was severely impaired in S1PR4-deficient animals. Splenic B cells showed reduced motility in the absence of S1PR4. However, titres of specific antibodies showed only minor reductions in S1PR4-deficient animals.DiscussionThese observations suggest that S1P signaling mediated by S1PR4 modifies chemokine-induced splenic B cell chemotaxis, thus modulating splenic microarchitecture, GC formation and T-cell dependent antibody production.

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Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players

Cited by 6 publications

References 98 publications

Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice

S1PR4 deficiency results in reduced germinal center formation but only marginally affects antibody production

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