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

Area of Science:

• Immunology
• Cell Biology
• Hematopoiesis

Background:

• Tissue-resident macrophages (Mφs) are traditionally thought to originate prenatally and self-maintain.
• Their origin and replenishment in adult tissues remain areas of active investigation.

Purpose of the Study:

• To identify and characterize novel progenitor cells in adult bone marrow that can differentiate into macrophages.
• To investigate the potential of these progenitors to replenish tissue-resident and inflammatory macrophage populations.

Main Methods:

• Flow cytometry and gene expression analysis were used to identify and characterize bone marrow progenitor cells.
• Tracking studies were performed to observe the migration and differentiation of these precursors in vivo.
• Transcriptomic analysis was employed to compare differentiated Mφs with existing populations.

Main Results:

• A progenitor population was identified in the early pro-B cell fraction of adult mouse bone marrow.
• These precursors coexpressed myeloid and lymphoid markers and had non-rearranged B-cell receptor genes.
• Upon exiting the bone marrow, these cells differentiated into tissue-resident Mφs in various organs and inflammatory Mφs at sites of inflammation, exhibiting distinct transcriptomes.

Conclusions:

• Bone marrow early pro-B cells represent a previously unrecognized source of macrophages in adult mice.
• These progenitors possess significant functional plasticity, differentiating into either tissue-resident or inflammatory Mφs based on microenvironmental cues.
• This finding challenges the established view of macrophage ontogeny and suggests a dynamic replenishment system in adults.