Identification of novel subsets of CD5+ B-1a cells reveals layered populations with distinct innate-like functions (67.2)

Abstract B-1a cells are found to contribute significantly to circulating natural antibodies and mucosal immunity as well as to immunoregulation. These various functional attributes of B-1a are often presented as reflecting the repertoire of all B-1a cells, while understanding how these functions are fulfilled at the clonal level is rather limited. Here we show that B-1a cells can be subdivided into two distinct stable subsets based on differing expression of the plasma cell alloantigen 1 (PC1), also known as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), an enzyme involved primarily in hydrolysis of ATP at the cell surface. One subset that we term PC1lo, expresses ENPP1 at low levels, whereas the second subset, designated PC1hi, expresses ENPP1 at high levels. These subsets are distinguishable by gene expression profiles, VH gene usage and time of development. Adoptively transferred PC1lo cells secret significantly more circulating natural IgM and intestinal IgA than PC1hi cells. In contrast, PC1hi cells produce more IL-10 than PC-1lo cells when stimulated with LPS and PMA. Furthermore, PC1lo cells generate antigen-specific IgM responses to pneumococcal polysaccharide antigens whereas PC1hi cells do not. We conclude that the classic B-1a functions segregate quite cleanly between these two subsets and the identification of PC1lo and PC1hi cells extends the concept of a layered immune system.