IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion

• DOI: 10.1182/blood.2023019721
• Publication Date: 2023-06-27T19:53:50Z
• Authors: Fabian M. P. Kaiser; Iga Janowska; Roberta Menafra; Melanie de Gier; Jakov Korzhenevich; Ingrid Pico-Knijn...; Indu Khatri; Ansgar Schulz; Taco W. Kuijpers; Arjan C. Lankester; Lukas Konstantinidis; Miriam Erlacher; Susan Kloet; Pauline A. van Sc...; Marta Rizzi; Mirjam van der Burg
• Keywords: Lymphopoiesis; Cell fate determination

Although absence of interleukin-7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, patients with severe combined immunodeficiency caused by mutations the IL-7 receptor α chain (IL-7Rα) still generate peripheral blood cells. Consequently, human has been thought to be independent signaling. Using flow cytometric analysis single-cell RNA sequencing bone marrow samples from healthy controls who are IL-7Rα deficient, combination vitro modeling B-cell differentiation, we demonstrate that IL-7R plays a crucial role lymphopoiesis. drives proliferation expansion early progenitors but not pre-BII large cells limited prevention cell death. Furthermore, guides fate decisions enhancing expression BACH2, EBF1, PAX5, which jointly orchestrate specification commitment progenitors. In line this observation, deficiency expressed myeloid-specific genes. Collectively, our results unveil previously unknown for promoting B-lymphoid expanding while defining important differences between mice humans. Our have implications hematopoietic stem transplantation strategies T- B+ provide insights into leukemogenesis.