B-1 cells and B-1 cell precursors prompt different responses to Wnt signaling

• Published in: PloS one 2018-06, Vol.13 (6), p.e0199332-e0199332
• Main Authors: Osugui, Lika, de Roo, Jolanda J, de Oliveira, Vivian Cristina, Sodré, Ana Clara Pires, Staal, Frank J T, Popi, Ana Flavia
• Format: Article
• Language: English
• Subjects: Animals; B cells; B-1 cells; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biological evolution; Biology and Life Sciences; Blood transfusions; Bone marrow; CD5 Antigens - metabolism; Cell culture; Cell division; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cell self-renewal; Evolutionary conservation; Female; Fetuses; Genes; Hematopoiesis; Hematopoietic stem cells; Immunology; Interleukin-7 - pharmacology; Kinases; Ligands; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine and Health Sciences; Mice, Inbred C57BL; Precursors; Receptors; Receptors, Interleukin-7 - metabolism; Research and Analysis Methods; Rodents; Signal transduction; Signaling; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Transcription factors; Wnt protein; Wnt proteins; Wnt Proteins - pharmacology; Wnt Signaling Pathway - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0199332

Recently several studies demonstrated a role for the Wnt pathway in lymphocyte development and self-renewal of hematopoietic stem cells (HSCs). B-1 cells constitute a separate lineage of B lymphocytes, originating during fetal hematopoiesis, expressing lymphoid and myeloid markers and possessing self-renewal ability, similar to early hematopoietic progenitors and HSCs. A plethora of studies have shown an important role for the evolutionary conserved Wnt pathway in the biology of HSCs and T lymphocyte development. Our previous data demonstrated abundant expression of Wnt pathway components by B-1 cells, including Wnt ligands and receptors. Here we report that the canonical Wnt pathway is activated in B-1 cell precursors, but not in mature B-1 cells. However, both B-1 precursors and B-1 cells are able to respond to Wnt ligands in vitro. Canonical Wnt activity promotes proliferation of B-1 cells, while non-canonical Wnt signals induce the expansion of B-1 precursors. Interestingly, using a co-culture system with OP9 cells, Wnt3a stimulus supported the generation of B-1a cells. Taking together, these results indicate that B-1 cells and their progenitors are differentially responsive to Wnt ligands, and that the balance of activation of canonical and non-canonical Wnt signaling may regulate the maintenance and differentiation of different B-1 cell subsets.