The Function of Themis2 in B Cells

Thymocyte-expressed molecule involved in selection 2 (Themis2) is the second member of the Themis family. Recently, the first member of the Themis family, Themis, has been reported to be part of the TCR signalling cascade and its deletion severely affects thymocyte progression from the double positive to the single positive stage. All family members share similar domains and high sequence similarity and show tissue specific expression with Themis2 being expressed in B lymphocytes, macrophages and dendritic cells. THEMIS2 associates with BCR signalling molecules such as GRB2, VAV or LYN and is phosphorylated in response to BCR stimulation. For these reasons I hypothesised that Themis2 might have an important role in B cell development or activation. I show that Themis2 is expressed throughout the B cell lineage and exclude redundant expression of other Themis family members. After B cell activation Themis2 expression is downregulated. Analysis of a newly created Themis2-deficient mouse strain showed that B cell development proceeds normally in the absence of THEMIS2. Experiments on in vitro cultured Themis2-deficient primary B cells demonstrated that proliferation and survival, BCR internalisation and antigen presentation as well as expression of activation markers and cytokines were unaffected. RNA sequencing revealed only minor changes in transcription in follicular B cells, even after activation. Similarly, antibody levels to in vivo immunisation with T-dependent or T-independent antigens or challenge with influenza virus did not suggest that Themis2 is required for antibody responses either. Reactions to a model of acute allergic airway inflammation showed only marginally reduced cell numbers in the bronchoalveolar lavage fluid yet all other markers of inflammation were all normal. In conclusion, I found that Themis2 is not required for B cell development, activation or antibody responses. Further studies will be required to define the role of Themis2 in the immune system

CRISPR-based strategies in infectious disease diagnosis and therapy

CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio

Themis2 is not required for B cell development, activation, and antibody responses

Themis1 is a protein implicated in transducing signals from the TCR. Mice deficient in Themis1 show a strong impairment in T cell selection in the thymus and defective T cell activation. The related Themis2 protein is expressed in B cells where it associates with signaling proteins Grb2 and Vav1, and is tyrosine phosphorylated after BCR stimulation. Thus, it has been proposed that Themis2 may transduce BCR signals, and hence play important roles in B cell development and activation. In this article, we show that Themis2 is expressed in all developing subsets of B cells, in mature follicular and marginal zone B cells, and in activated B cells, including germinal center B cells and plasma cells. In contrast, B lineage cells express no other Themis-family genes. Activation of B cells leads to reduced Themis2 expression, although it remains the only Themis-family protein expressed. To analyze the physiological function of Themis2, we generated a Themis2-deficient mouse strain. Surprisingly, we found that Themis2 is not required for B cell development, for activation, or for Ab responses either to model Ags or to influenza viral infection