The Role of B Cells in Primary Progressive Multiple Sclerosis
The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.680581/full |
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| author | Jameson P. Holloman Robert C. Axtell Robert C. Axtell Nancy L. Monson Nancy L. Monson Gregory F. Wu Gregory F. Wu |
| author_facet | Jameson P. Holloman Robert C. Axtell Robert C. Axtell Nancy L. Monson Nancy L. Monson Gregory F. Wu Gregory F. Wu |
| author_sort | Jameson P. Holloman |
| collection | DOAJ |
| description | The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it's unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS. |
| first_indexed | 2024-12-16T11:45:03Z |
| format | Article |
| id | doaj.art-e44f89348c0a427dae1caa8ff29e2439 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-16T11:45:03Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e44f89348c0a427dae1caa8ff29e24392022-12-21T22:32:51ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-06-011210.3389/fneur.2021.680581680581The Role of B Cells in Primary Progressive Multiple SclerosisJameson P. Holloman0Robert C. Axtell1Robert C. Axtell2Nancy L. Monson3Nancy L. Monson4Gregory F. Wu5Gregory F. Wu6Department of Neurology, Washington University in St. Louis, St. Louis, MO, United StatesDepartment of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesDepartment of Microbiology and Immunology, Oklahoma University Health Science Center, Oklahoma City, OK, United StatesDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, United StatesDepartment of Immunology, University of Texas Southwestern, Dallas, TX, United StatesDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, United StatesDepartment of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United StatesThe success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it's unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS.https://www.frontiersin.org/articles/10.3389/fneur.2021.680581/fullB cellmultiple sclerosisimmune pathogenesisinflammationprimary progressive multiple sclerosis |
| spellingShingle | Jameson P. Holloman Robert C. Axtell Robert C. Axtell Nancy L. Monson Nancy L. Monson Gregory F. Wu Gregory F. Wu The Role of B Cells in Primary Progressive Multiple Sclerosis Frontiers in Neurology B cell multiple sclerosis immune pathogenesis inflammation primary progressive multiple sclerosis |
| title | The Role of B Cells in Primary Progressive Multiple Sclerosis |
| title_full | The Role of B Cells in Primary Progressive Multiple Sclerosis |
| title_fullStr | The Role of B Cells in Primary Progressive Multiple Sclerosis |
| title_full_unstemmed | The Role of B Cells in Primary Progressive Multiple Sclerosis |
| title_short | The Role of B Cells in Primary Progressive Multiple Sclerosis |
| title_sort | role of b cells in primary progressive multiple sclerosis |
| topic | B cell multiple sclerosis immune pathogenesis inflammation primary progressive multiple sclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.680581/full |
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