Myelin-reactive B cells exacerbate the severity of CD4 <sup>+</sup> T cell-driven CNS autoimmunity in an IL-23-dependent manner
Bibliographic record
Abstract
Abstract Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) that has traditionally been considered a T cell-mediated disease. However, accumulating evidence points to a crucial role for B cells in disease processes. IgH [MOG] mice possess a transgenic immunoglobulin heavy chain derived from a monoclonal antibody specific to myelin oligodendrocyte glycoprotein (MOG), a key target for autoimmune responses. Here, using the experimental autoimmune encephalomyelitis (EAE) model of MS, we investigated the susceptibility of IgH [MOG] mice to CD4 + T cell-driven disease that was induced by active immunization with MOG [35-55] autoantigen. We found that immunized IgH [MOG] mice rapidly developed severe EAE, characterized by the aggregation of T and B cells in the CNS meninges. We observed an increased presence of class-switched and inflammatory cytokine-positive B cells in the IgH [MOG] CNS, as well as a greater frequency of IL-17- and GM-CSF-producing CD4 + T cells. Production of the Th17 maintenance factor IL-23 was increased from IgH [MOG] CNS-infiltrating B cells, and in vivo blockade of IL-23p19 strongly attenuated disease severity in IgH [MOG] mice. Strikingly, we observed an increased frequency of PD-1 + CXCR5 - T peripheral helper (Tph)-like cells in the CNS parenchyma and dura mater of IgH [MOG] mice. Both Tph accumulation in the CNS, as well as meningeal inflammation, were again sharply reduced upon IL-23p19 blockade in vivo . Notably, CNS-infiltrating B and Tph cells from IgH [MOG] mice showed an upregulation of genes related to neurodegeneration and oxidative phosphorylation, and IL-23 blockade reduced ROS production from these cells in vivo . Altogether, these data show that MOG-specific B cells contribute to severe CD4 + T cell-driven EAE by promoting CNS accumulation of Th17 and Tph cells, as well as tertiary lymphoid organs in the CNS meninges, in an IL-23 dependent manner.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".