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The role of TIA1 and TIAL1 in germinal center B cell function and survival

Cellular & Molecular Immunology volume 20, pages 1090–1092 (2023)Cite this article

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A recently published study revealed the essential role of TIA1 and TIAL1 in promoting the survival of GC B cells by regulating the expression of the prosurvival protein MCL1 [10]. These findings provide valuable insights into the role of TIA1 and TIAL1 in driving GC B cell responses and shaping the processes underlying the critical role of RBPs in regulating B cell fate after affinity maturation (Fig. 1). To understand the function of TIA1 and TIAL1 in GC B cells, the authors generated mice with conditional knockout of TIA1 and TIAL1 and found that the generation of antigen-specific GC B cells was severely impaired in Tial and Tial1 double knockout (dKO) mice compared to control mice. Consistent with this finding, the production of high-affinity antibodies, especially IgG1 homologous antibodies, induced by the thymus-dependent antigen NP-KLH was significantly reduced in mice lacking TIA1 and TIAL1.

To reveal the molecular mechanisms controlled by TIA1 and TIAL1 in GC B cells, researchers have combined global transcriptomic analysis with the UV crosslinking and immunoprecipitation (iCLIP) technique. Transcriptomic analyses of TIA1- and TIAL1-deficient GC B cells revealed the profound impact of TIA1 and TIAL1 on gene expression profiles. Interestingly, the transcriptomes of Tia1 and Tial1 dKO GC B cells exhibited characteristics that more closely resembled those of GC B cells from the LZ than those of GC B cells from the DZ, indicating the failure of gene expression modification in Tia1 and Tial1 dKO GC B cells during the transition from the LZ to DZ. Flow cytometric analyses showed that the expression levels of MHC class II molecules and key components of the PI3K pathway were unaltered in Tia1 and Tial1 dKO GC B cells, indicating that the capacities for antigen capture, antigen presentation, and B cell activation remained normal in the absence of TIA1 and TIAL1. Although pathway analysis revealed changes in ROS metabolism, DNA damage, and p53-related signaling in Tia1 and Tial1 dKO GC B cells, the results of further experiments suggested that TIA1 and TIAL1 are dispensable for the biological processes described above. In Tia1 and Tial1 dKO GC B cells, neither induction of the transcription factor MYC, a key molecular event during positive selection in the DZ, nor cell cycle progression was affected. These findings suggest that TIA1 and TIAL1 play limited roles in the aforementioned processes in GC B cells.

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Fig. 1

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Acknowledgements

The current work was supported by a special program from the Ministry of Science and Technology of China (2022YFA1105200 and 2021YFA1101000), the Chinese National Natural Science Funds (U20A20393, 32125016, 31925013, 31870902 and 32070907), and Gusu Innovation Leading Talent Program (ZXL2022505).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215123, China

    Yongqiang Wang & Jisheng Liu

  2. Institutes of Biology and Medical Science, Soochow University, Suzhou, 215123, China

    Yongqiang Wang & Fangfang Zhou

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YW drafted the manuscript and drew the figure. JL and FZ provided valuable discussion and revised the manuscript.

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Correspondence to Jisheng Liu or Fangfang Zhou.

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Wang, Y., Liu, J. & Zhou, F. The role of TIA1 and TIAL1 in germinal center B cell function and survival. Cell Mol Immunol 20, 1090–1092 (2023). https://doi.org/10.1038/s41423-023-01067-0

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