Commensal microbes drive the generation of large numbers of bone marrow plasma cells

The mechanisms whereby enteric pathogens and microbes induce systemic antibody responses remain obscure. In contrast to accepted models, we show that commensal microbes have a dramatic impact on the bone marrow (BM) plasma cell pool. Unlike standard vendor mice, in mice reared in our colony the majority of long-lived BM plasma cells secreted IgA antibodies. Exposing vendor mice to a unique microflora or Helicobacter sp. led to the generation of IgA-secreting BM cells, while also inducing increases in serum IgA antibodies enriched for binding to several commensal bacterial taxa. Moreover, BM IgA-secreting plasma cells exhibited a common clonal ancestry with intestinal IgA+ plasma cells, and both populations possessed unique gene expression signatures compared to other long-lived BM plasma cells. We conclude that commensal microbes overtly influence the BM plasma cell pool, and suggest that select commensal microbes can facilitate the induction of systemic humoral immunity. Cells were sorted from B6.BlimpGFP reporter mice isolated from the bone marrow, lamina propria, or the spleen of naïve mice housed under SPF conditions. Plasma cells from the bone marrow were sorted based on viability, Dump-(CD4, CD8, F4/80, Ter119), IgD-, CD138+, Blimp+, and then either IgA+, IgM+, or IgA-IgM-. Plasma cells from the gut were sorted based on a surface phenotype of Dump-, IgD-, B220-, Blimp+, and IgA+. The cells were sorted two times to ensure greater purity. Replicate numbers for the plasma cell samples indicate the cells came from the same mouse. The follicular B cells were sorted from different mice from the spleen and had a phenotype of CD19+, B220+, CD23+, CD21-, and IgD+.