A Novel Role of Complement in Mobilization: Immunodeficient Mice Are Poor Granulocyte-Colony Stimulating Factor Mobilizers Because They Lack Complement-Activating Immunoglobulins
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Bibliographic record
Abstract
Complement (C) and innate immunity emerge as important and underappreciated modulators of mobilization of hematopoietic stem/progenitor cells (HSPC). We reported that (a) C becomes activated in bone marrow (BM) during granulocyte-colony-stimulating factor (G-CSF)-induced mobilization by the classic immunoglobulin (Ig)-dependent pathway and that (b) C3 cleavage fragments increase the responsiveness of HSPC to a stromal derived factor-1 gradient. Since patients suffering from severe combined immunodeficiency (SCID) mobilize poorly, we hypothesized that this could be directly linked to the lack of C activating Ig in these patients. In the current study to better elucidate the role of C activation in HSPC mobilization, we mobilized mice that lack Ig (RAG2, SCID, and Jh) by G-CSF or zymosan, compounds that activate C by the classic Ig-dependent and the alternative Ig-independent pathways, respectively. In addition, we evaluated mobilization in C5-deficient animals. Mobilization was evaluated by measuring the number of colony-forming unit-granulocyte macrophage and leukocytes circulating in peripheral blood. We found that (a) G-CSF- but not zymosan-induced mobilization was severely reduced in RAG2, SCID, and Jh mice; (b) impaired G-CSF-induced mobilization was restored after infusion of purified wild-type Ig; and (c) mobilization was severely reduced in C5-deficient mice. These data provide strong evidence that the C system plays a pivotal role in mobilization of HSPC and that egress of HSPC from BM occurs as part of an immune response. Disclosure of potential conflicts of interest is found at the end of this article.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it