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Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress
- Source :
- Haematologica
- Publication Year :
- 2019
-
Abstract
- Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IκB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.
- Subjects :
- Myeloid
IκB kinase
Biology
Article
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Animals
B cell
030304 developmental biology
Adaptor Proteins, Signal Transducing
0303 health sciences
B-Lymphocytes
Macrophages
Hematopoietic Stem Cell Transplantation
Signal transducing adaptor protein
Myeloid leukemia
Hematology
Cell biology
Transplantation
Haematopoiesis
medicine.anatomical_structure
030220 oncology & carcinogenesis
Bone marrow
Signal Transduction
Subjects
Details
- ISSN :
- 15928721
- Volume :
- 106
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....a09aac05a80c837f4231c18b298d1fcd