B Cells Are Essential for Proteinuria Induction in a Mouse Model of Autoimmune Idiopathic Nephrotic Syndrome
Bibliographic record
Abstract
Background: The idiopathic nephrotic syndrome (INS) is defined by heavy proteinuria, hypoalbuminemia, and edema. This occurs when the kidney’s specialized epithelial cell, the podocyte, is injured by mechanisms that are still unknown. The recent discovery of autoantibodies targeting podocyte proteins like nephrin and Crb2 in human patients hints at the role of B cells and autoantibodies in INS, but their exact role is still unclear. Our objective is to establish if B cells are essential for the induction of proteinuria in a mouse model of autoimmune INS. Methods: As previously published (Hada et al., J Am Soc Nephrol, 2022), 19 C3H/HeN mice were immunized three times at 2-wks intervals with recombinant Crb2, a transmembrane protein expressed at the podocyte slit diaphragm. One week after the first immunization, 10 mice received anti-CD20 (MB-11, BioXCell) to deplete B cells and 9 an isotype control. Serum and urine were tested for anti-Crb2 antibody and albuminuria, respectively. Inguinal lymph nodes and spleens were immunophenotyped at 6 wks. Results: Mice that received anti-CD20 (‘treated’) showed a 95% decrease in circulating CD19+ B cells at 2 and 4 wks. At 6 wks, no treated mice (0/10) developed INS compared to 88% (8/9) of the mice receiving the isotype control (‘control’). Anti-Crb2 antibody titers were lower in treated mice (1591±759 vs. 7207±3985 µg/mL, p<0.003). In the inguinal lymph nodes of treated mice, a respective 50% and 80% decrease in the number of CD4+ and CD19+ cells (p<0.001) were observed compared to controls. This was driven by a 75% decrease in switched memory B cells (CD19+ IgD- IgM- IgG+; p<0.005). The germinal centers in the inguinal lymph nodes of treated mice were reduced in size (p<0.007) and showed a reduced number of IgG+ positive B cells (p<0.003). Conclusion: These results suggest that autoantibody-producing B cells are essential for proteinuria induction in this mouse model of autoimmune INS. Moreover, their role may not be limited to autoantibody production, as their crosstalk with T cells is likely significant. A better understanding of these mechanisms is crucial to develop targeted treatments for patients with autoimmune INS. Funding: Private Foundation Support, Government Support – Non-U.S.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".