Oct2 and Obf1 as Facilitators of B:T Cell Collaboration during a Humoral Immune Response

Corcoran, Lynn M.; Emslie, Dianne; Kratina, Tobias; Shi, Wei; Hirsch, Steffen; Taubenheim, Nadine; Chevrier, Stéphane

doi:10.3389/fimmu.2014.00108

Cited by 27 publications

(26 citation statements)

References 80 publications

(110 reference statements)

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“…The proximal components of TCR form a multiprotein complex including ZAP‐70/Syk and Lck, and Bob1 in Tfh cells can thus modulate TCR signalosomes including Syk to appropriately adjust cellular responses . While it is known that Bob1 and Bcl‐6 can upregulate Syk in B cells, further investigation is needed to determine the role of Bob1 and Bcl‐6 in the control of Syk in Tfh cells .…”

Section: Discussionmentioning

confidence: 99%

Bob1 limits cellular frequency of T‐follicular helper cells

et al. 2016

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T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B‐cell lymphoma‐6 and Blimp‐1 determine lineages of Tfh cells and other types of effector CD4+ T cells, respectively, suggests that there are unique mechanisms to establish Tfh‐cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B‐cell lymphoma‐6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1−/− mice were much higher than those in wild‐type (WT) mice. In addition, expansion of Tfh cells within Bob1−/−CD4+ T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T‐cell‐intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1−/− Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3‐induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1‐related mechanism to restrict numerical frequency against stimulation of TCRs.

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Section: Discussionmentioning

confidence: 99%

Bob1 limits cellular frequency of T‐follicular helper cells

et al. 2016

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“…However, IgM + MBCs were also enriched for many genes proposed to regulate or inhibit B cell activation, such as FCRLA, FCRL2, FCRL3, CBLB, CD72 and SIGLEC10 (Wu and Bondada, 2009, Sohn et al, 2003, Meyer et al, 2018, Kochi et al, 2009, Shabani et al, 2014), which may reflect a fine regulatory balance controlling their activation threshold. Perhaps underpinning this, unswitched MBCs also expressed higher levels of the transcription factor genes POU2F2 (OCT2) and FOXP1 than class-switched MBCs (Figure 5F), which coordinate the capacity of B cells to respond normally to antigen receptor signals and directly repress key regulators of plasma cell differentiation respectively (van Keimpema et al, 2015, Corcoran et al, 2014). This is consistent with switched IgG + MBCs being more likely to differentiate into plasma cells, while unswitched IgM + MBCs are more likely to re-enter or form secondary GC responses to gain higher affinity (Dogan et al, 2009, Lutz et al, 2015, Seifert et al, 2015).…”

Section: Resultsmentioning

confidence: 96%

Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation

King

Orban

Riches

et al. 2020

Preprint

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15In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce 16 mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states 17 and their antibody-based selection is challenging to decipher in primary human tissue. We have applied 18 an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics 19 of human B cells undergoing affinity maturation. We define unique gene expression and antibody 20 repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo 21 class switch recombination. We dissect antibody class-dependent gene expression of germinal centre 22 and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B 23 cells to undergo antibody-based selection and differentiate. Together, our analyses provide 24 unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated 25 immunity. 26 27 121 122 157 sampling of IgH sequences from bulk repertoires to enhance genotype correction, identification of 158

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“…Aff3 is a rheumatoid arthritis susceptibility gene that also influences the response to anti-TNF treatment (Tan et al, 2010). The function of POU2F2 in B cell differentiation was extensively studied and shown to mediate the physical interaction of B and T cells (Corcoran et al, 2014); however, its role in Th cell differentiation has not been described. In our network, the expression of Pou2f2 was increased in the early and late stages of Th2 cell differentiation compared to naïve T cells.…”

Section: Novel and Potentially Important Tfs For Th2 Cell Fate Decisionsmentioning

confidence: 99%

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

et al. 2016

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ABSTRACT. Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.

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Oct2 and Obf1 as Facilitators of B:T Cell Collaboration during a Humoral Immune Response

Cited by 27 publications

References 80 publications

Bob1 limits cellular frequency of T‐follicular helper cells

Bob1 limits cellular frequency of T‐follicular helper cells

Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

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