Abstract 250: Four-And-A-Half LIM Domain Protein 2 Plays a Critical Role in Spleen T-Cell Dependent Antibody Response
Bibliographic record
Abstract
Background: Four-and-a-half LIM domain protein 2 (FHL2) is an adaptor molecule that regulates signalling cascades and gene transcription. We have uncovered vasculoprotective and atheroprotective effects of FHL2 knockout in mice. Since B cells could regulate these processes, we investigated the potential role of FHL2 in B cell function and activity. Methods and Results: Under basal conditions, FHL2-/- mice presented a mild splenomegaly (84.0±9.0 vs 68.0±5.0mg), associated with bigger spleen follicles (1.6 fold) and higher proportions of spleen B cells (56.0±2.0 vs 40.0±9.0%) vs WT mice. Flow cytometry confirmed significantly higher (p<0.05) proportions of B cells in the follicles (Fo)(CD23+CD21lo/int) (77.0±1.0 vs 67.0±3.0%) and the marginal zone (Mz)(CD23-,CD21+)(7.0±1.0 vs 2.5±1.0%) of FHL2-/- vs WT mice. Mice were injected with sheep red blood cells (SRBC) to elicit a T cell-dependent B cell activation. SRBC did not influence Fo and Mz B cell numbers, but it did affect germinal center (GC) formation. GCs are zones within Fo where T cells activate B cells to produce high affinity antibodies. SRBC induced a 5- and 2.5-fold increase in B cells (GL7+) within FHL2-/- and WT GCs, respectively. However, there was no increase in plasma IgG1 levels in FHL2-/- mice in response to SRBC, whereas a 3-fold increase was observed in WT mice (1158±227 vs 2943±226ng/ml; p<0.05). Instead, plasma IgM levels were higher in FHL2-/- than WT SRBC mice. Moreover, SRBC only induced a modest, 1.3-fold fold increase in Fo T helper cells (CXCR5+PD1+) in FHL2-/- compared with a 6-fold increase in WT. Nevertheless, FHL2-/- B cells successfully proliferated and underwent class switch recombination in response to LPS, anti-CD40 and IL-4 in vitro, indicating that these cells were not defective. Conclusion: These results suggest that FHL2 plays a critical role in spleen antibody production in response to a T-dependent antigen, possibly by affecting activation or antigen presentation by Fo T helper cells.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.003 |
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".