The role of serine metabolism in B lymphocytes
The serine synthesis pathway (SSP) has been identified as highly upregulated in metabolically active cells and feeds into 1C metabolism, helping to generate biosynthetic material for cell proliferation and cell survival. The SSP in the context of GC B cells has not been previously explored, and ther...
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| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1826309743135686656 |
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| author | Khan, A |
| author2 | Clarke, A |
| author_facet | Clarke, A Khan, A |
| author_sort | Khan, A |
| collection | OXFORD |
| description | The serine synthesis pathway (SSP) has been identified as highly upregulated in metabolically active cells and feeds into 1C metabolism, helping to generate biosynthetic material for cell proliferation and cell survival. The SSP in the context of GC B cells has not been previously explored, and therefore, I sought to determine its role. I found no effect on proliferation or viability of serine and glycine deprivation on wild type B cells. I identified upregulation of the SSP during activation in replete media, which was further amplified when depriving B cells of serine and glycine. Immunoglobulin production is relatively decreased when stimulated B cells are cultured without serine and glycine. However, using B cell conditional phosphoglycerate dehydrogenase (PHGDH) knockout mice, following immunisation, there was a relative increase in IgG1+ GC B cells. When I activated and cultured B cells from Phgdh KO mouse in vitro, I also found a relative increase in IgG1+ B cells. Phgdh KO mouse B cells did not survive or proliferate without serine and glycine in vitro. Together, my findings indicate that the SSP, as well as serine and glycine availability, is involved in B cell proliferation and viability, as well as in the molecular control of immunoglobulin expression. These findings could help in understanding ways in which the SSP can be manipulated for clinical treatment of cancers and autoimmune disease. |
| first_indexed | 2024-03-07T07:40:16Z |
| format | Thesis |
| id | oxford-uuid:fcc323f0-0680-4639-beb7-ee023c30b9ae |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:40:16Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:fcc323f0-0680-4639-beb7-ee023c30b9ae2023-04-05T14:45:35ZThe role of serine metabolism in B lymphocytesThesishttp://purl.org/coar/resource_type/c_bdccuuid:fcc323f0-0680-4639-beb7-ee023c30b9aeMolecular immunologyExperimental immunologyBiochemistryImmunologyEnglishHyrax Deposit2022Khan, AClarke, ASimon, KThe serine synthesis pathway (SSP) has been identified as highly upregulated in metabolically active cells and feeds into 1C metabolism, helping to generate biosynthetic material for cell proliferation and cell survival. The SSP in the context of GC B cells has not been previously explored, and therefore, I sought to determine its role. I found no effect on proliferation or viability of serine and glycine deprivation on wild type B cells. I identified upregulation of the SSP during activation in replete media, which was further amplified when depriving B cells of serine and glycine. Immunoglobulin production is relatively decreased when stimulated B cells are cultured without serine and glycine. However, using B cell conditional phosphoglycerate dehydrogenase (PHGDH) knockout mice, following immunisation, there was a relative increase in IgG1+ GC B cells. When I activated and cultured B cells from Phgdh KO mouse in vitro, I also found a relative increase in IgG1+ B cells. Phgdh KO mouse B cells did not survive or proliferate without serine and glycine in vitro. Together, my findings indicate that the SSP, as well as serine and glycine availability, is involved in B cell proliferation and viability, as well as in the molecular control of immunoglobulin expression. These findings could help in understanding ways in which the SSP can be manipulated for clinical treatment of cancers and autoimmune disease. |
| spellingShingle | Molecular immunology Experimental immunology Biochemistry Immunology Khan, A The role of serine metabolism in B lymphocytes |
| title | The role of serine metabolism in B lymphocytes |
| title_full | The role of serine metabolism in B lymphocytes |
| title_fullStr | The role of serine metabolism in B lymphocytes |
| title_full_unstemmed | The role of serine metabolism in B lymphocytes |
| title_short | The role of serine metabolism in B lymphocytes |
| title_sort | role of serine metabolism in b lymphocytes |
| topic | Molecular immunology Experimental immunology Biochemistry Immunology |
| work_keys_str_mv | AT khana theroleofserinemetabolisminblymphocytes AT khana roleofserinemetabolisminblymphocytes |