Bone marrow basophils enhance immature B cell survival by recruitment and contact dependent signals

Abstract

Abstract B cell development in the bone marrow relies upon an organized tissue structure. Maturing progenitors migrate between several distinct niches and towards the sinusoidal vessels before entering circulation. Microenvironments specific for early developmental stages are provided by stroma expressing CXCL12 (pre-pro-B), IL-7 (pro-B), or Galactin-1 (pre-B); however, the identity of a defined niche for immature B cells remains unclear. A DX5+Thy1lo cell has been shown to provide IgM+ progenitors survival signals through direct cell-cell contact; but the cell type responsible, factors provided, and the influence this help may have on B cell function remains unknown. Here, utilizing in vitro B cell selection assays and in vivo depletion experiments, we identify the DX5+Thy1lo cells as basophils. We demonstrate that this population produces chemotactic factors, which act to recruit immature B cells and therefore enable provision of pro-survival signals directly via cell-cell contact. Furthermore, the bone marrow basophil population expanded during the first 24 hours following induction of inflammation by injection of Freund’s incomplete adjuvant. This response correlated with an increase in the number of immature B cells within the marrow, as well as, a reduction of lambda light chain usage in the immature but not mature B cell population. These results reveal that bone marrow basophils actively provide a supportive microenvironment for immature B cells and that the sensitivity of basophils to inflammatory stimuli may modulate BCR repertoire development.