Infection with non-CD4 tropic variant of SIVmac239 accelerates the formation of mature germinal center reactions and elicits antigen specific B cell responses
Bibliographic record
Abstract
Abstract Background What determines the development of germinal centers (GCs) in lymph nodes (LNs) early after HIV/SIV infection is likely to be crucial for developing neutralizing antibodies and B cell memory. Materials and Methods Rhesus macaques were inoculated i.v. with either SIVmac239 (n=2) or iMac239ΔD385 (iMacΔD) (n=4), a CD4-independent variant of SIVmac239 lacking a CD4 binding site (J. Virol. 90:4966, 2016). LNs from different time points were analyzed using polychromatic flow cytometry and multiplexed confocal imaging. Results In contrast to SIVmac239, iMacΔD infection was associated with relative preservation of total and CD28hiCD95hi memory CD4 T cells, consistent with its compromised capacity to target CD4 T cells. Imaging analysis revealed accelerated formation of mature, polarized GCs in iMacΔD compared to SIVmac239 infected animals, a profile associated with i) increased frequencies of PD-1hiBcl-6hi CD4 T cells, ii) higher levels of IL-10 and IL-21 within the follicles, iii) increased frequency of PH2AX+ (a required factor for isotype switching) B cells, iv) lower levels of Fas-L in the follicular areas, associated with lower TUNEL (cell death) positivity and v) lower accumulation of CD163+ cells (monocytes/macrophages; a surrogate of local inflammation) in proximity to follicles. The observed GC dynamics associate with earlier virus-specific antibody responses in iMacΔD compared to SIVmac239. Conclusions Our data indicate that CD4 tropism of SIV greatly affects the development of GC reactions early after infection. The iMacΔD model could provide critical information on how GC reactions can be manipulated to augment the generation of neutralizing antibodies and B cell memory.
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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) | 0.000 | 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 | 0.000 |
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".