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Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 12/4/2012, Vol. 109 Issue 49, p20077-20082, 6p
- Publication Year :
- 2012
-
Abstract
- 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<superscript>lo</superscript> and B-1a.PC1<superscript>hi</superscript>, differ significantly in IgH chain utilization. Adoptively transferred PC1<superscript>lo</superscript> cells secreted significantly more circulating natural IgM and intestinal IgA than PC1<superscript>hi</superscript> cells. In contrast, PC1<superscript>hi</superscript> cells produced more IL-10 than PC1<superscript>lo</superscript> cells when stimulated with LPS and phorbol 12-myristate 13-acetate (PMA). PC1<superscript>hi</superscript> cells were also more efficient than PC1<superscript>lo</superscript> cells in regulating Th1 cell differentiation, even though both B-1a subsets were comparably active in stimulating T-cell proliferation. Furthermore, PC1<superscript>lo</superscript> cells generated antigen-specific IgM responses to pneumococcal polysaccharide antigens, whereas PC1<superscript>hi</superscript> cells do not. We found that PC1<superscript>hi</superscript> cells develop from an early wave of B-1a progenitors in fetal life, whereas ~ cells are generated from a later wave afterbirth. We conclude that identification of B-1a.PC1<superscript>lo</superscript> and B-1a.PC1<superscript>hi</superscript> cells extends the concept of a layered immune system with important implications for developing effective vaccines and promoting the generation of immunoregulatory B cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 109
- Issue :
- 49
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 84040735
- Full Text :
- https://doi.org/10.1073/pnas.1212428109