B Cells from Blood of Patients with Relapsing-Remitting Multiple Sclerosis Induce Apoptosis in Neurons <i>In Vitro</i> (P1.177)
Bibliographic record
Abstract
OBJECTIVE: Determine if supernatants (Sup) from multiple sclerosis (MS) and normal control (NC) B cells are cytotoxic for neurons in vitro and characterize mechanisms of any observed cytotoxicity. BACKGROUND: B cells are important in MS pathogenesis independent of maturation into antibody producing cells. We reported that B cells from relapsing-remitting MS (RRMS) patients but not NC secreted factors cytotoxic for oligodendrocytes in vitro. Cytotoxicity was not related to the presence of IgM or IgG nor dependent on complement activation. We hypothesized that B cell Sup from RRMS but not NC would also be toxic to neurons, mediated, in part, by apoptosis. DESIGN/METHODS: Neonatal rat brain cultures contained 85% neurons, 10% astrocytes and 5% microglia. Circulating B cells from 7 RRMS patients and 7 NC were cultured (48-96 hours) without additional stimulation. Sup diluted 1:4 with neuronal culture medium were incubated with neuronal cultures for 72 hours. Cell death was determined by trypan blue uptake. Serum in all media was heat inactivated. IgM and IgG levels were previously determined in Sup of 3 NC and 3 MS. Apoptosis was determined by TUNEL staining. RESULTS: Media alone (B cell medium diluted 1:4 with neuronal medium) was non-toxic. B cell Sup from NC induced neuronal death of 8.4% (0-29%), whereas values for MS Sup were 46.6% (37-63%); p<0.001. IgG was detected in only one Sup (NC) and no Sup had detectable IgM. MS Sup greatly increased apoptosis in neurons compared to NC. CONCLUSIONS: MS B cell Sup induce neuronal death to a much greater extent than NC Sup. Neuronal death was independent of IgG and IgM, not mediated by complement activation and occurred at least partially by apoptosis. B cells found in the meninges could be particularly important in mediating demyelination and neuronal/axonal damage in subpial cortical MS lesions. Study Supported by: Parker Webber Endowment (WSU/DMC Foundation); Mary Parker Neuroscience Fund (DMC Foundation); Multiple Sclerosis Society of Canada; Canadian Institutes of Health Research
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".