Journal Club: Immunology, Tissue Engineering, and Biochemistry

IMMUNOLOGY: Integrin-mediated interactions between B cells and follicular dendritic cells influence germinal center B cell fitness. Wang, X., et al. (Cyster). J Immunol. 2014 Apr 16. Epub ahead of print.

During an infection, many B cells head to lymph node structures called germinal centers and undergo rounds of mutation and selection such that they produce higher-affinity antibodies. 

This process is known to require interactions between B cells and follicular dendritic cells. In vitro studies have shown this interaction involves two particular integrin heterodimers on B cells, but their importance in vivo had not been determined.

In this paper, Wang and colleagues found that while removal of a single heterodimer had no effect, removal of both heterodimers resulted in less efficient B cell responses in germinal centers when competing with wildtype B cells. Simultaneous removal of both VCAM1 from follicular dendritic cells and a single heterodimer from B cells had a similar effect.

TISSUE ENGINEERING: Effect of collagen nanotopography on keloid fibroblast proliferation and matrix synthesis: implications for dermal wound healing. Muthusubramaniam, L. et al. (Desai). Tissue Eng Part A. 2014 Apr 11. Epub ahead of print.

Most of the time, a scar is at worst mildly unsightly. For a minority of individuals, however, it can lead to a keloid, in which the scar tissue grows beyond—sometimes far beyond—the site of the original insult. Keloids can be painful and difficult to treat. 

Previous studies have found that cells in a keloid undergo more proliferation at the edge than in the center. The edge borders normal skin that contains unaligned collagen fibers, whereas in the middle of the keloid most of the collagen fibers are aligned.

In this paper, the authors seeded keloid and normal fibroblasts into different collagen scaffolds. They found that keloid fibroblasts in the presence of aligned rather than random fibrils had lower expression of genes associated with cell proliferation and collagen production. They plan to investigate whether collagen-containing dermal patches may be an effective therapy.  

BIOCHEMISTRY: Hst3 is turned over by a replication stress-responsive SCF-Cdc4 phospho-degron. Edenberg, E.R., et al. (Toczyski). PNAS. 2014 Apr 8. Epub ahead of print.

In eukaryotes, DNA associates with a set of proteins called histones. A variety of chemical modifications to these histones have critical biological functions. Acetylation of lysine 56 of histone 3 (H3K56ac) is important in DNA replication and repair in yeast.

Previous research revealed that precise, rapid changes in the amount of the protein Hst3, which removes the H3K56ac modification, are essential. It was known that varying Hst3 transcription contributed to these changes but less clear if post-transcriptional mechanisms were also involved.  

Here, Edenberg and colleagues reported that Hst3 is targeted for degradation by SCF-Cdc4 through recognition of two short stretches containing phosphorylated amino acids. They further observed that these same recognition sites were also required for replication stress-induced increases in Hst3 degradation.

CELL ENGINEERING: Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal. Park, J.S., et al. (Lim, W.). PNAS. 2014 Apr 7. Epub ahead of print.

Precise homing of specific cells plays an essential role in a host of biological processes, from immune reactions to germ cell development, and an ability to direct cell migration would be a powerful tool.

G-coupled protein receptors frequently play a role in stimulating cell movement. Recently, various such receptors have been modified to no longer respond to their natural ligands but instead to an artificial molecule.

In this paper, members of the Lim lab demonstrated use of such a receptor to control cell migration. Expression of the modified receptor allowed several different cell types to respond to the artificial ligand. Furthermore, T cells engineered to express the receptor homed to a subcutaneous implant of the ligand in a mouse, suggesting this technology might one day have therapeutic applications.