B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1

Abstract

Transcriptional activator Oct2 and cofactor OBF-1 regulate B cell IL-6 to induce T cell production of IL-21, to support Tfh cell development in antiviral immunity.

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

“…In contrast, these organs were repopulated by comparable numbers of Pou2af1 −/− and Pou2af1 +/+ CD4 + T cells (Fig 4A). In line with the recent observation that the development of GC B cells is hampered in Pou2af1 −/− mice (Karnowski et al , 2012), we observed a significant reduction in the frequency and numbers of FAS + GL7 + GC B cells within the population of Pou2af1 −/− B cells in the BM chimeras upon immunization with SRBCs (Figs 4B and EV1A). The most striking observation was, however, a defect in the development of Tfh cells from mature, recirculating Pou2af1 −/− CD4 + T cells in these experiments.…”

“…Along this line, Karnowski et al (2012) have recently reported that Pou2af1 −/− CD4 + T cells are not impaired in their ability to differentiate into Tfh cells during influenza infection in mice reconstituted with wild‐type B cells. Viral infections, however, elicit strong Toll‐like receptor signals not only in DCs and B cells, but also in CD4 + T cells that, depending on the pathogenic stimulus and the anatomic compartment, promote the generation of Tfh cells and adaptive immune responses (Hou et al , 2011; Rookhuizen & Defranco, 2014; Kubinak et al , 2015).…”

“…In contrast, only 9% (spleen), 6% (MLN), and 13% (PP) of the CXCR5 hi ICOS + Tfh cells from Pou2af1 −/− mice expressed similar levels of Bcl6 (Fig 6A). To exclude the possibility that the reduction in Bcl6 expression is secondary to B‐cell defects in Bob1‐deficient mice, such as the impaired secretion of IL‐6 (Karnowski et al , 2012), we analyzed Bcl6 expression in wild‐type and knockout Tfh cells from Pou2af1 −/− : Pou2af1 +/+ mixed bone marrow chimeras—generated as described in the previous section—7 days after immunization with SRBC. In line with the results obtained with Pou2af1 −/− mice (Fig 6A), we observed an impaired differentiation of Bob1‐deficient CD4 + T cells into CXCR5 hi ICOS + Bcl6 hi Tfh cells in the bone marrow chimeras (Fig 6B).…”

“…Still, the induction of Tfh signature genes such as Bcl6 and CXCR5 is not yet fully understood. Bcl6 expression appears to be governed by ICOS ligation and DC‐derived cytokines that signal via signal transducer and activator of transcription 3 (STAT3) including interleukin‐6 (IL‐6), IL‐27 and later on by autocrine stimulation via IL‐21 (Batten et al , 2010; Eto et al , 2011; Harker et al , 2011; Karnowski et al , 2012; Choi et al , 2013). Earlier studies suggested that Bcl6 drives CXCR5 expression (Johnston et al , 2009; Nurieva et al , 2009; Yu et al , 2009); however, more recent data indicate that the expression of genes important for the relocation of Tfh cells from the T cell‐rich areas to the B‐cell follicles—foremost Cxcr5 —is initiated independently of Bcl6 by the transcription factor Ascl2 (Liu et al , 2012, 2014b).…”

Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8 + T cells

“…Littermate and DM2 mice were infected with influenza A virus and DTX was administered on days 7-9 of infection (Fig. 5A) during the expansion and differentiation of CD8 + T cells, GC B cells, and Tfh cells (27,28). The medLNs, lung, and spleen were analyzed on day 10 for the CD8 + T-cell responses; the Tfh, and B-cell responses were measured in the medLNs only.…”