Phenotype Of Innate Immune Cells Research Articles

The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers

To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2(MUT) mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2(MUT) antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells. However, these cells fail to complete early GC-commitment differentiation and coalesce as nascent GC aggregates. Bcl6 directly binds and represses trafficking receptors S1pr1 and Gpr183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B cell migration and may contribute to GC failure in Bcl6RD2(MUT) mice. The development of functional GC-TFH cells was partially impaired in Bcl6RD2(MUT) mice. In contrast to Bcl6(-/-) mice, Bcl6RD2(MUT) animals experience no inflammatory disease or macrophage deregulation. These results reveal an essential role for RD2 repression in early GC commitment and striking biochemical specificity in Bcl6 control of humoral and innate immune-cell phenotypes.

Innate Immune Cell–Derived Microparticles Facilitate Hepatocarcinoma Metastasis by Transferring Integrin αMβ2 to Tumor Cells

Mechanisms by which tumor cells metastasize to distant organs still remain enigmatic. Immune cells have been assumed to be the root of metastasis by their fusing with tumor cells. This fusion theory, although interpreting tumor metastasis analogically and intriguingly, is arguable to date. We show in this study an alternative explanation by immune cell-derived microparticles (MPs). Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell migration in vitro and metastasis in vivo. The underlying molecular basis was involved in integrin α(M)β₂ (CD11b/CD18), which could be effectively relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking either CD11b or CD18 led to significant decreases in MP-mediated tumor cell metastasis. This MP-mediated transfer of immune phenotype to tumor cells might also occur in vivo. These findings suggest that tumor cells may usurp innate immune cell phenotypes via MP pathway for their metastasis, providing new insight into tumor metastatic mechanism.

Monitoring peri-operative immune suppression in renal cancer patients

The aim of this study was the identification of surrogate markers of host immunity in renal cell carcinoma (RCC) patients. Using 4-color flow cytometry the immunophenotype of blood immune cells of RCC patients was compared to that of healthy volunteers and correlated with staging and grading of patients. Furthermore, the time course of these immune markers was compared in RCC patients undergoing either open surgery or laparoscopy. Compared to the healthy control group, blood of RCC patients contained more granulocytes and higher percentages of CTLA4+CD8+ T lymphocytes, but reduced numbers of dendritic cells (DCs) and of CD28+ CD8+ T cells. Tumor progression was associated with a higher white blood cell count, a reduced frequency of blood DCs and increased numbers of CD57+ T and NK cells. Monocytes of patients with advanced RCC showed a reduced HLA-DR surface expression associated with higher aminopeptidase N(APN)/CD13 expression. Tumor surgery caused an increase of granulocytes and a decrease of all lymphocytic and DC subpopulations within 24 h, whereas the number of HLA-DR low monocytes was up-regulated. As demonstrated by time kinetic analysis, laparoscopic intervention caused a more moderate immunosuppression and an enhanced restoration of immune activity than open surgery. These results suggest that the composition and the phenotype of innate immune cells reflect well the differences in the cellular immunity of RCC patients associated with tumor disease as well as surgery. The monocytic HLA-DR intensity represents a suitable marker for monitoring tumor stage and surgery-associated immunosuppression in RCC patients.