B1-like innate B cells are present in adult human organs in homeostasis.

Innate-like B cells produce natural antibodies and include marginal zone (MZ) B cells and B1 cells. B1 cells are well characterized in mice, where they prenatally seed serous cavities and produce regulatory cytokines. Putative B1 cells have been identified in human prenatal organs, but whether they persist into adulthood remains unclear. Here, we identified B1-like cells in the IgM+ and IgA+ memory compartment across adult human organs. These cells transcriptionally resembled murine and human prenatal B1 cells but not MZ B cells. They expressed canonical murine B1 cell markers, including AHNAK, and spontaneously secreted IgM. B cell receptor sequencing of paired kidney-spleen samples revealed lower diversity and mutation rates in kidney IgM/IgA clones, suggesting spleen-independent seeding. Adult B1-like cells expressed the regulatory cytokine TGFB and had abundant inferred interactions with tissue myeloid cells, which reciprocally expressed B cell prosurvival cytokines. These findings support the presence of B1-like cells across adult human organs in homeostasis.