Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral B lymphocytes in humans and is associated with a variety of malignancies and proliferative disorders. Latent membrane protein 2A (LMP2A) is one of only two viral proteins expressed in latently infected B lymphocytes in vivo. LMP2A blocks B cell receptor (BCR) signal transduction in vitro by binding the Syk and Lyn protein tyrosine kinases. To analyze the significance of LMP2A expression in vivo, transgenic mice with B cell lineage expression of LMP2A were generated. LMP2A expression results in the bypass of normal B lymphocyte developmental checkpoints allowing immunoglobulin-negative cells to colonize peripheral lymphoid organs, indicating that LMP2A possesses a constitutive signaling activity in nontransformed cells.

Thiol-ene photopolymerization offers a unique platform for the formation of peptide-functionalized poly(ethylene glycol) hydrogels and the encapsulation, culture and differentiation of cells. Specifically, this photoinitiated polymerization scheme occurs at neutral pH and can be controlled both spatially and temporally. Here, we have encapsulated human mesenchymal stem cells (hMSCs) in matrix metalloproteinase (MMP) degradable and cell-adhesive hydrogels using thiol-ene photopolymerization. We find that hMSCs survive equally well in this system, regardless of MMP-degradability. When hMSCs are encapsulated in these cell-degradable hydrogels, they survive and are able to proliferate. In classic hMSC differentiation medias, hMSCs locally remodel their microenvironment and take on characteristic morphologies; hMSCs cultured in growth or osteogenic differentiation media are less round, as measured by elliptical form factor, and are smaller than hMSCs cultured in chondrogenic or adipogenic differentiation media. In addition, hMSCs encapsulated in completely cell-degradable hydrogels and cultured in osteogenic, chondrogenic, or adipogenic differentiation media generally express increased levels of specific differentiation markers as compared to cells in hydrogels that are not cell-degradable. These studies demonstrate the ability to culture and differentiate hMSCs in MMP-degradable hydrogels polymerized via a thiol-ene reaction scheme and that increased cell-mediated hydrogel degradability facilitates directed differentiation of hMSCs.

The lymphocyte‐specific protein tyrosine kinase p56lck participates in T cell signaling through functional interactions with components of the T cell antigen receptor complex and the interleukin‐2 receptor. Additional insight into the function of p56lck has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56lckR273). Mice bearing the lckR273 transgene manifested a severe defect in the production of virtually all T lymphocytes. Those exceptional CD3+ cells that escaped the effects of the lckR273 transgene were confined primarily to the T cell subset that expresses gamma/delta T cell receptors. Remarkably, construction of a dose‐response curve for the effects of the lckR273 transgene revealed that developmental arrest of thymocytes occurred at a discrete stage in the normal T cell maturation pathway, corresponding to a point at which thymoblasts ordinarily begin a series of mitotic divisions that result in expansion and maturation. These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts.