Glycan Remodelling Controls Germinal Centre B cell Responses
Bibliographic record
Abstract
Abstract Germinal centre (GC) B cells are routinely identified through distinct changes on their surface carbohydrates, called glycans; yet, whether these modifications play an essential role in GC reaction remain unknown. One striking change relates to the monosaccharide sialic acid. In mice, this change is mediated through downregulation of an enzyme called Cmah. As a consequence, GC B cells lose the preferred ligand for CD22, a member of the sialic acid-binding immunoglobulin-type lectins (Siglecs) and a co-inhibitory receptor of the B cell antigen receptor. Since CD22 regulates B cell function, we hypothesize that this specific glycan remodelling on B cells control the GC reaction by modulating the activity of CD22. To test our hypothesis, we developed a mouse model that constitutively expresses Cmah in B cells. Following immunization, we find that sustained expression of Cmah in B cells results in impaired generation of antigen-specific GC B cells. More significantly, this observed defect is dependent on CD22, highlighting that coordinated loss of preferred ligands for CD22 on B cells plays a critical function in the GC. Furthermore, antibody affinity maturation is significantly impaired in immunized mice harbouring B cells which lack either CD22 or its cis glycan ligands, further supporting the role of CD22 and its glycan ligands in the GC. Ongoing efforts are focused on defining the GC-specific nature of these observations and examining potential mechanism related to BCR signalling, GC B cell survival and exit to plasma cells, and B-T cell interactions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".