B cells develop from hematopoietic stem cells through an interplay of transcriptional networks and microenvironmental cues. Regulation of B cell development is critical for the generation of a pathogen-reactive antibody repertoire, as well as prevention of B cell malignancy and autoimmunity. Expression of the unconventional myosin family protein Myo18A starts in early B cell progenitors and increases continuously throughout B cell development. B cell-specific deletion of Myo18A (Myo18A BKO) leads to a significant expansion of bone marrow B cells. Pseudotime analysis of single cell RNA sequencing data in control Mb1cre/+ and Myo18A BKO bone marrow cells revealed that the developmental path of B cells is unaffected in the absence of Myo18A. However, scCODA-based compositional analysis and flow cytometry showed expansion of small pre-B cells in Myo18A BKO bone marrow. These data suggest that pre-B cell numbers are restricted by Myo18A. Differential gene expression analysis showed altered expression of genes encoding transcription factors, ribosomal, mitochondrial and cytoskeletal proteins in small pre-B cells of Myo18A BKO mice. Mechanistically, Myo18A BKO small pre-B cells exhibited greater migration along CXCL12 gradients. These data establish a novel role Myo18A in controlling B cell development through regulation of gene expression and migratory behavior.
The unconventional myosin family protein Myo18A is a novel regulator of B cell development
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Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1