Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions
2012
Wang, Hongsheng | Shin, Dong-Mi | Abbasi, Sadia | Jain, Shweta | Kovalchuk, Alexander L. | Beaty, Natalie | Suofei, | Gonzalez-Garcia, Ines | Morse, Herbert C.
Innate-like B-1a cells contribute significantly to circulating natural antibodies and mucosal immunity as well as to immunoregulation. Here we show that these classic functions of B-1a cells segregate between two unique subsets defined by expression of plasma cell alloantigen 1 (PC1), also known as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1). These subsets, designated B-1a.PC1 ˡᵒ and B-1a.PC1 ʰⁱ, differ significantly in IgH chain utilization. Adoptively transferred PC1 ˡᵒ cells secreted significantly more circulating natural IgM and intestinal IgA than PC1 ʰⁱ cells. In contrast, PC1 ʰⁱ cells produced more IL-10 than PC1 ˡᵒ cells when stimulated with LPS and phorbol 12-myristate 13-acetate (PMA). PC1 ʰⁱ cells were also more efficient than PC1 ˡᵒ cells in regulating Th1 cell differentiation, even though both B-1a subsets were comparably active in stimulating T-cell proliferation. Furthermore, PC1 ˡᵒ cells generated antigen-specific IgM responses to pneumococcal polysaccharide antigens, whereas PC1 ʰⁱ cells do not. We found that PC1 ˡᵒ cells develop from an early wave of B-1a progenitors in fetal life, whereas PC1 ʰⁱ cells are generated from a later wave after birth. We conclude that identification of B-1a.PC1 ˡᵒ and B-1a.PC1 ʰⁱ cells extends the concept of a layered immune system with important implications for developing effective vaccines and promoting the generation of immunoregulatory B cells.
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