Aire is a cell-intrinsic regulator of natural IgM-secreting cells.

Aire intrinsically limits natural IgM-secreting cells, especially IgM+ cells, revealing a new role beyond thymic T cell tolerance.

• Why it matters: Understanding how natural IgM-secreting cells are regulated is crucial for insights into immune homeostasis and autoimmune prevention, addressing gaps beyond thymic tolerance mechanisms.
• What they did: The study examined Aire expression in spleen and bone marrow antibody-secreting cells, focusing on IgM+ cells derived mainly from B-1a and marginal zone B cells, using in vitro and in vivo analyses.
• The result: Aire does not induce promiscuous gene expression but intrinsically constrains the number of natural IgM-secreting cells, highlighting its role in maintaining immune balance rather than self-tolerance.