Press releases
Please quote Nature Immunology as the source of these items.
The July 2007 issue of Nature Immunology is available online.
July 2007
Checking immune activation
Armed 'killer' cells can re-enter lymph nodes to destroy dendritic cells — a specialized type of immune cell — according to a report published this week online in Nature Immunology. Such killing by antigen-specific T cells reduces further priming of naive immune cells of similar specificity, thereby preventing excessive immune cell activation. The results overturn prevailing notions that lymph nodes provide restrictive environments that prevent entry of activated T cells.
Sallusto and colleagues show 'resting' lymph nodes continue to bar entry to previously activated immune 'killer' cells called effector memory CD8+ T cells. Upon inflammatory signals that occur during infection, however, lymph nodes are activated and transiently express a chemical signal called CXCL9 and recruits memory T cells directly from the bloodstream. These memory cells express a receptor called CXCR3 that recognizes CXCL9.
In addition to checking further immune activation, the CXCL9 entry pathway provides a means to combat pathogens, including viruses such as HIV that replicate in lymph node tissues. The study should also be instructive to those working toward more effective vaccine development and improving efficacy.
L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells
Greta Guarda, Miroslav Hons, Silvia F Soriano, Alex Y Huang, Rosalind Polley, Alfonso Mart�n-Fontecha, Jens V Stein, Ronald N Germain, Antonio Lanzavecchia & Federica Sallusto
Published online: 27 May 2007 | doi 10.1038/ni1469
Regulating insensitivity to DNA damage
A protein commonly associated with B cell lymphomas suppresses elimination of �useful� B cells that otherwise harbor damaged DNA, suggests a report published online this week in Nature Immunology.
In most cells, DNA damage triggers �sensors� to halt cellular activity until the DNA damage is repaired. Ari Melnick and colleagues find that the protein Bcl-6 prevents the production of the DNA damage sensor, called ATR, in a select group of B cells called germinal center (GC) cells, which produce antibodies. In this setting Bcl-6 is beneficial to B cells that encounter foreign antigen and then undergo highly focused DNA mutations in antibody-encoding genes, a process normally required to generate highly effective antibodies. However, such DNA mutations can also lead to GC B cell death, potentially reducing the production of useful antibodies.
Melnick's group shows that Bcl-6 can suppress activity of the ATR gene, which effectively 'turns off' the DNA damage sensor machinery and leaves the mutated GC B cells less prone to DNA damage-induced death. More generally, many B cell lymphomas display deregulated Bcl-6 expression and tolerate excessive DNA mutations, including those generated by radiation treatments. The new work suggests that manipulating Bcl-6 in lymphoma cells might render them more sensitive to irradiation.
Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR
Stella Maris Ranuncolo, Jose M Polo, Jamil Dierov, Michael Singer, Tracy Kuo, John Greally, Roland Green, Martin Carroll & Ari Melnick
Published online: 10 June 2007 | doi 10.1038/ni1478
Dialling down 'natural' antibody production
Researchers have identified a molecule that reduces production of antibodies by a specialized set of immune cells reports a paper online this week in Nature Immunology.
Lars Nitschke and colleagues discovered Siglec-G (sialic acid binding immunoglobulin-like lectin) is highly expressed in a subset of antibody-producing cells called B1 B cells. These cells arise early in life and produce weak antibodies, often called 'natural' antibodies that can recognize many different antigens including 'self-tissues'. Siglec-G acts to desensitize these B1 cells by damping down signalling pathways within these cells when triggered by antigen contact. Mice lacking Siglec-G have higher numbers of B1 cells and substantially more 'natural' antibodies in their blood, including autoantibodies known as rheumatoid factors. Thus, Siglec-G acts as a brake to reduce the potential for excessive antibody production.
The findings point to a possible risk factor for developing autoimmunity disease should mutations arise in the gene encoding Siglec-G that alter its function.
Siglec-G is a B1 cell—inhibitory receptor that controls expansion and calcium signaling of the B1 cell population
Anja Hoffmann, Sheena Kerr, Julia Jellusova, Jiquan Zhang, Florian Weisel, Ute Wellmann, Thomas H Winkler, Burkhard Kneitz, Paul R Crocker & Lars Nitschke
Published online: 17 June 2007 | doi 10.1038/ni1480
