Contribution of DOCK11 to the Expansion of Antigen-Specific Populations among Germinal Center B Cells

Sakamoto, Akihiko; Maruyama, Mitsuo

doi:10.4049/immunohorizons.2000048

Cited by 6 publications

(5 citation statements)

References 57 publications

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“…Pax5 encodes the B-cell lineage-specific activator protein, which affects B-cell differentiation at the early stages ( Arseneau et al, 2009 ). DOCK11 regulates B-cell activation during immunization ( Sakamoto & Maruyama, 2020 ). TBX21 is known as a regulator of immune cell development and function ( Stolarczyk, Lord & Howard, 2014 ), while IL-10 has been shown to modulate inflammatory responses and is particularly important in maintaining intestinal microbe-immune homeostasis ( Neumann, Scheffold & Rutz, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated omics analysis reveals the immunologic characteristics of cystic Peyer’s patches in the cecum of Bactrian camels

Wang

et al. 2023

PeerJ

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Bactrian camels have specific mucosa-associated lymphoid tissue (MALT) throughout the large intestine, with species-unique cystic Peyer’s patches (PPS) as the main type of tissue. However, detailed information about the molecular characteristics of PPS remains unclear. This study applied a transcriptomic analysis, untargeted metabolomics, and 16S rDNA sequencing to compare the significant differences between PPS and the adjacent normal intestine tissues (NPPS) during the healthy stage of three young Bactrian camels. The results showed that samples from PPS could be easily differentiated from the NPPS samples based on gene expression profile, metabolites, and microbial composition, separately indicated using dimension reduction methods. A total of 7,568 up-regulated and 1,266 down-regulated differentially expressed genes (DEGs) were detected, and an enrichment analysis found 994 DEGs that participated in immune-related functions, and a co-occurance network analysis identified nine hub genes (BTK, P2RX7, Pax5, DSG1, PTPN2, DOCK11, TBX21, IL10, and HLA-DOB) during multiple immunologic processes. Further, PPS and NPPS both had a similar pattern of most compounds among all profiles of metabolites, and only 113 differentially expressed metabolites (DEMs) were identified, with 101 of these being down-regulated. Deoxycholic acid (DCA; VIP = 37.96, log2FC = −2.97, P = 0), cholic acid (CA; VIP = 13.10, log2FC = −2.10, P = 0.01), and lithocholic acid (LCA; VIP = 12.94, log2FC = −1.63, P = 0.01) were the highest contributors to the significant dissimilarities between groups. PPS had significantly lower species richness (Chao1), while Firmicutes (35.92% ± 19.39%), Bacteroidetes (31.73% ± 6.24%), and Proteobacteria (13.96% ± 16.21%) were the main phyla across all samples. The LEfSe analysis showed that Lysinibacillus, Rikenellaceae_RC9_gut_group, Candidatus_Stoquefichus, Mailhella, Alistipes, and Ruminococcaceae_UCG_005 were biomarkers of the NPPS group, while Escherichia_Shigella, Synergistes, Pyramidobacter, Odoribacter, Methanobrevibacter, Cloacibacillus, Fusobacterium, and Parabacteroides were significantly higher in the PPS group. In the Procrustes analysis, the transcriptome changes between groups showed no significant correlations with metabolites or microbial communities, whereas the alteration of metabolites significantly correlated with the alteration of the microbial community. In the co-occurrence network, seven DEMs (M403T65-neg, M329T119-neg, M309T38-neg, M277T42-2-neg, M473T27-neg, M747T38-1-pos, and M482t187-pos) and 14 genera (e.g., Akkermansia, Candidatus-Stoquefichus, Caproiciproducens, and Erysipelatoclostridium) clustered much more tightly, suggesting dense interactions. The results of this study provide new insights into the understanding of the immune microenvironment of the cystic PPS in the cecum of Bactrian camels.

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Section: Discussionmentioning

confidence: 99%

Integrated omics analysis reveals the immunologic characteristics of cystic Peyer’s patches in the cecum of Bactrian camels

Wang

et al. 2023

PeerJ

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“…Consistently, we also described that adoptive transfer of cognate T cells recovered the impaired recall responses of antigen-experienced B cells in DOCK11-deficient mice. We have recently demonstrated that the lack of DOCK11 in B cells is involved in the impaired induction of T follicular helper, T FH cells upon immunization [ 11 ]. These T cells are an interesting and indispensable population since it has been known that these cells were found to provide cognate help in recall responses of memory B cells [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…We successively demonstrated that DOCK11 was associated with bone marrow B cell development and marginal zone B cell formation [ 10 ]. In addition to this function, we recently also found that DOCK11 potentially contributes to the expansion of antigen-specific populations among GC B cells upon immunization [ 11 ]. Mechanistically, the lack of DOCK11 resulted in the attenuation of B cell-intrinsic signaling.…”

Section: Introductionmentioning

confidence: 99%

The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells

et al. 2022

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Background Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses. Results In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells. Conclusions We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.

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“…Moreover, DOCK11, a mediator of cytokinesis, is another contributor of immunosenescence during ageing, although independent of B cell antibody responses [ 38 ]. For instance, mice with DOCK11-deificient B cells have reduced antigen-specific participation in germinal centers, which is accompanied by lower B cell intrinsic-signaling stimulation [ 39 ]. Furthermore, the interleukin-1 converting enzyme CASP1, is a protease which converts the inactive form of IL-1Β to its active form, that is a precursor of inflammatory processes [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants

et al. 2022

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Background Perturbations in the composition and diversity of the gut microbiota are accompanied by a decline in immune homeostasis during ageing, characterized by chronic low-grade inflammation and enhanced innate immunity. Genetic insights into the interaction between age-related alterations in the gut microbiota and immune function remain largely unexplored. Methods We investigated publicly available transcriptomic gut profiles of young germ-free mouse hosts transplanted with old donor gut microbiota to identify immune-associated differentially expressed genes (DEGs). Literature screening of the Gene Expression Omnibus and PubMed identified one murine (Mus musculus) gene expression dataset (GSE130026) that included small intestine tissues from young (5–6 weeks old) germ-free mice hosts that were compared following 8 weeks after transplantation with either old (~ 24-month old; n = 5) or young (5–6 weeks old; n = 4) mouse donor gut microbiota. Results A total of 112 differentially expressed genes (DEGs) were identified and used to construct a gut network of encoded proteins, in which DEGs were functionally annotated as being involved in an immune process based on gene ontology. The association between the expression of immune-process DEGs and abundance of immune infiltrates from gene signatures in normal colorectal tissues was estimated from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project. The analysis revealed a 25-gene signature of immune-associated DEGs and their expression profile was positively correlated with naïve T-cell, effector memory T-cell, central memory T-cell, resident memory T-cell, exhausted T-cell, resting Treg T-cell, effector Treg T-cell and Th1-like colorectal gene signatures. Conclusions These genes may have a potential role as candidate markers of immune dysregulation during gut microbiota ageing. Moreover, these DEGs may provide insights into the altered immune response to microbiota in the ageing gut, including reduced antigen presentation and alterations in cytokine and chemokine production.

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Contribution of DOCK11 to the Expansion of Antigen-Specific Populations among Germinal Center B Cells

Cited by 6 publications

References 57 publications

Integrated omics analysis reveals the immunologic characteristics of cystic Peyer’s patches in the cecum of Bactrian camels

Integrated omics analysis reveals the immunologic characteristics of cystic Peyer’s patches in the cecum of Bactrian camels

The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells

Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants

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