Human Transitional And Igm(Low) Mature Naive B Cells Preserve Permissive B-Cell Receptors

The level of immunoglobulin M (IgM) displayed on the surface of peripheral blood B cells exhibits a broad dynamic range and has been associated with both development and selection. To determine whether IgM surface expression associates with distinct immunoglobulin heavy-chain (IGH) repertoire properties, we performed deep IgM sequencing of peripheral blood transitional and mature naive B cells in the upper and lower quartiles of surface IgM expression for 12 healthy donors. Mature naive B cells within the lowest quartile for surface IgM expression displayed more diverse IGH features including increased complementarity-determining region 3 length, IGHJ6 segment usage and aromatic amino acids compared with mature naive B cells with high surface IgM. There were no differences between IGH repertoires for transitional B cells with high or low surface IgM. These findings suggest that a selection checkpoint during progression of transitional to mature naive B cells reduces the breadth of the IGH repertoire among high surface IgM B cells but that diversity is preserved in B cells expressing low levels of surface IgM.