Novel in vitro model for high-rate IgA class switching.

Mcintyre, T. M.; Kehry, Marilyn R.; Snapper, Clifford M.

doi:10.4049/jimmunol.154.7.3156

Cited by 105 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, both the G/C and hotspot targeting are much higher in GL 5′Sμ segments amplified from cells induced with LPS + IL‐4 than with LPS ± anti‐δ dextran (Tables II and III). It is known that IL‐4 treatment can increase CSR without increasing GL transcript levels (Shockett and Stavnezer, 1991; McIntyre et al ., 1995). Perhaps IL‐4 increases the size of the region targeted by AID, resulting in introduction of mutations at G/C base pairs and hotspots over a greater region, although the frequency of mutation in the GL 5′Sμ region was not increased in cells treated with LPS + IL‐4 (Table I, row 6).…”

Section: Discussionmentioning

confidence: 99%

Mutations occur in the Ig S region but rarely in S regions prior to class switch recombination

et al. 2003

View full text Add to dashboard Cite

Nucleotide substitutions are found in recombined Ig switch (S) regions and also in unrecombined (germline, GL) Sm segments in activated splenic B cells. Herein we examine whether mutations are also introduced into the downstream acceptor S regions prior to switch recombination, but ®nd very few mutations in GL Sg3 and Sg1 regions in activated B cells. These data suggest that switch recombination initiates in the Sm segment and secondarily involves the downstream acceptor S region. Furthermore, the pattern and speci®city of mutations in GL and recombined Sm segments differ, suggesting different repair mechanisms. Mutations in recombined Sm regions show a strong bias toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into the GL Sm do not. Additionally, induction conditions affect mutation speci®city within the GL Sm segment. Mutations are most frequent near the S±S junctions and decrease rapidly with distance from the junction. Finally, we ®nd that mice expressing a transgene for terminal deoxynucleotidyl transferase (TdT) have nucleotide insertions at S±S junctions, indicating that the recombining DNA ends are accessible to end-processing enzyme activities.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutations occur in the Ig S region but rarely in S regions prior to class switch recombination

et al. 2003

View full text Add to dashboard Cite

show abstract

“…When exogenous cytokines including IL-2 and IL-10 or IL-10 and TGF-β are additionally treated, induction of differential regulation of IgG1 and IgG3 was observed. Other studies also revealed that mitogen [ 72 ] and virulent factors including Staphylococcus aureus Cowan and lipopolysaccharide [ 66 , 67 , 73 – 75 ] can be promising stimulant factors for in vitro IgA production in human PBMC or B cell line [ 75 ]. Table 2 shows the IgA CSR factors and their working mechanism inducing IgA CSR in B cells.…”

Section: Modeling Iga Production In Vitromentioning

confidence: 99%

“…B , C high-rate IgA class switching of B cells obtained from spleen induced by dual combinations of the multivalent antigen receptor crosslinker, aδ-dex, CD40L, and/or LPS, plus IL-4 + IL-5, in the presence or absence of TGF-β. The percentages of membrane IgA positive (mIgA + ) cells were analyzed using flow cytometry [ 67 ] …”

Section: Modeling Iga Production In Vitromentioning

confidence: 99%

Intestinal Peyer’s Patches: Structure, Function, and In Vitro Modeling

Park

Cho

Kang

2023

Tissue Eng Regen Med

View full text Add to dashboard Cite

Backgound: Considering the important role of the Peyer’s patches (PPs) in gut immune balance, understanding of the detailed mechanisms that control and regulate the antigens in PPs can facilitate the development of immune therapeutic strategies against the gut inflammatory diseases. Methods: In this review, we summarize the unique structure and function of intestinal PPs and current technologies to establish in vitro intestinal PP system focusing on M cell within the follicle-associated epithelium and IgA + B cell models for studying mucosal immune networks. Furthermore, multidisciplinary approaches to establish more physiologically relevant PP model were proposed. Results: PPs are surrounded by follicle-associated epithelium containing microfold (M) cells, which serve as special gateways for luminal antigen transport across the gut epithelium. The transported antigens are processed by immune cells within PPs and then, antigen-specific mucosal immune response or mucosal tolerance is initiated, depending on the response of underlying mucosal immune cells. So far, there is no high fidelity (patho)physiological model of PPs; however, there have been several efforts to recapitulate the key steps of mucosal immunity in PPs such as antigen transport through M cells and mucosal IgA responses. Conclusion: Current in vitro PP models are not sufficient to recapitulate how mucosal immune system works in PPs. Advanced three-dimensional cell culture technologies would enable to recapitulate the function of PPs, and bridge the gap between animal models and human.

show abstract

“…It was reported to decrease proliferation of B cells and to increase apoptosis of immature or resting B cells in mice and humans (160)(161)(162)(163). Furthermore, TGF-b can inhibit immunoglobulin synthesis and class switching in IgG isotypes and promotes the production of IgA in mice and humans (164)(165)(166).…”

Section: B Cellsmentioning

confidence: 99%

Lymphocyte Immunosuppression and Dysfunction Contributing to Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS)

Bergmann

Beckmann

Salyer

et al. 2020

Shock

View full text Add to dashboard Cite

Persistent Inflammation, Immune Suppression, and Catabolism Syndrome (PICS) is a disease state affecting patients who have a prolonged recovery after the acute phase of a large inflammatory insult. Trauma and sepsis are two pathologies after which such an insult evolves. In this review, we will focus on the key clinical determinants of PICS: Immunosuppression and cellular dysfunction. Currently, relevant immunosuppressive functions have been attributed to both innate and adaptive immune cells. However, there are significant gaps in our knowledge, as for trauma and sepsis the immunosuppressive functions of these cells have mostly been described in acute phase of inflammation so far, and their clinical relevance for the development of prolonged immunosuppression is mostly unknown. It is suggested that the initial immune imbalance determines the development of PCIS. Additionally, it remains unclear what distinguishes the onset of immune dysfunction in trauma and sepsis and how this drives immunosuppression in these cells. In this review, we will discuss how regulatory T cells (Tregs), innate lymphoid cells, natural killer T cells (NKT cells), TCR-a CD4 À CD8 À doublenegative Tcells (DN Tcells), and B cells can contribute to the development of post-traumatic and septic immunosuppression. Altogether, we seek to fill a gap in the understanding of the contribution of lymphocyte immunosuppression and dysfunction to the development of chronic immune disbalance. Further, we will provide an overview of promising diagnostic and therapeutic interventions, whose potential to overcome the detrimental immunosuppression after trauma and sepsis is currently being tested.

show abstract

Novel in vitro model for high-rate IgA class switching.

Cited by 105 publications

References 0 publications

Mutations occur in the Ig S region but rarely in S regions prior to class switch recombination

Mutations occur in the Ig S region but rarely in S regions prior to class switch recombination

Intestinal Peyer’s Patches: Structure, Function, and In Vitro Modeling

Lymphocyte Immunosuppression and Dysfunction Contributing to Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS)

Contact Info

Product

Resources

About