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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Troilo, A; Wehr, C; Janowska, I; Venhoff, N; Thiel, J; Rawluk, J; Frede, N; Staniek, J; Lorenzetti, R; Schleyer, MT; Herget, GW; Konstantinidis, L; Erlacher, M; Proietti, M; Camacho-Ordonez, N; Voll, RE; Grimbacher, B; Warnatz, K; Salzer, U; Rizzi, M.
Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency.
Blood. 2020; 135(17): 1452-1457.
Doi: 10.1182/blood.2019003855
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- Co-authors Med Uni Graz
- Thiel Jens
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- Abstract:
- Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.
- Find related publications in this database (using NLM MeSH Indexing)
- B-Lymphocytes - immunology, pathology
- Bone Marrow - immunology, pathology
- Cell Differentiation - administration & dosage
- Common Variable Immunodeficiency - etiology, pathology
- Hematopoiesis - administration & dosage
- Humans - administration & dosage
- Lymphocyte Activation - immunology
- Prognosis - administration & dosage