Hartweger, H; (2015) The Function of Themis2 in B Cells. Doctoral thesis , UCL (University College London).

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Abstract

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.

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