Pre/pro-B cells generate macrophage populations during homeostasis and inflammation

Abstract

Most tissue-resident macrophages (Mφs) are believed to be derived prenatally and are assumed to maintain themselves throughout life by self-proliferation. However, in adult mice we identified a progenitor within bone marrow, early pro-B cell/fraction B, that differentiates into tissue Mφs. These Mφ precursors have non-rearranged B-cell receptor genes and coexpress myeloid (GR1, CD11b, and CD16/32) and lymphoid (B220 and CD19) lineage markers. During steady state, these precursors exit bone marrow, losing Gr1, and enter the systemic circulation, seeding the gastrointestinal system as well as pleural and peritoneal cavities but not the brain. While in these tissues, they acquire a transcriptome identical to embryonically derived tissue-resident Mφs. Similarly, these Mφ precursors also enter sites of inflammation, gaining CD115, F4/80, and CD16/32, and become indistinguishable from blood monocyte-derived Mφs. Thus, we have identified a population of cells within the bone marrow early pro-B cell compartment that possess functional plasticity to differentiate into either tissue-resident or inflammatory Mφs, depending on microenvironmental signals. We propose that these precursors represent an additional source of Mφ populations in adult mice during steady state and inflammation.

The biology of serous cavity macrophages

“…An alternative mechanism for the replenishment of serous cavity F4/80 hi macrophages has been proposed recently. Audzevich et al [45] have suggested that macrophages can also arise from pre/pro-B cells in both peritoneal and pleural cavities. By using the Mb1 iCre .Rosa26 LSL-eYFP strain to fate-map B cell progenitors, high levels of labelling were detected in peritoneal and pleural macrophages, but not in most other tissue macrophages under steady state conditions.…”

The Origins and Functions of Tissue-Resident Macrophages in Kidney Development

“…Recently, another bone marrow-derived source of adult macrophage progenitors has been discovered (Audzevich et al, 2017 ). These cells are bi-phenotypic early pro-B cells that express both myeloid and lymphoid markers.…”

“…These cells are bi-phenotypic early pro-B cells that express both myeloid and lymphoid markers. Like HSC-derived monocytes, early pro-B cells exit the bone marrow, travel through the circulation, and contribute to certain tissue-resident macrophage populations (such as in the peritoneum, pleural cavity, and intestine) during tissue homeostasis and inflammation (Audzevich et al, 2017 ).…”

Parallels between vertebrate cardiac and cutaneous wound healing and regeneration

“… 91 , 92 However, subsequent findings suggest that this may be too simplistic and that more pro-inflammatory as well as pro-regenerative macrophage subsets may exist and that differentiation of these is governed by their local microenvironment. 89 , 101 It is becoming clear that macrophage subtypes have vital and somewhat contradictory roles during tissue repair and that the careful balance of these different phenotypic states will be crucial for allowing full tissue regeneration. 16 , 51 , 54 , 55 , 87 – 90 , 96 , 100 , 102 – 104 Macrophage subsets have recently been identified in zebrafish 105 and suggested to contribute to aspects of larval fin regeneration and wound angiogenesis (see section 'Re-vascularisation' below), 106 , 107 but further investigation will be required to determine the origin of these different subtypes and if pro-regenerative populations are enriched following skin or cardiac injury in fish, contributing to the regenerative capacity of these organs.…”