Role of B cell receptor signaling in IL-10 production by normal and malignant B-1 cells.

Autor: Alhakeem SS; Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky., Sindhava VJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., McKenna MK; Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky., Gachuki BW; Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky., Byrd JC; Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio., Muthusamy N; Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio., Bondada S; Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2015 Dec; Vol. 1362, pp. 239-249. Date of Electronic Publication: 2015 Jun 11.
DOI: 10.1111/nyas.12802
Abstrakt: B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. However, we found that CLL cells appear to be unique in not responding to IL-10-mediated feedback-suppressive effects in comparison to normal B-1 cells. In addition, we describe a novel role of the BCR signaling pathway in constitutive IL-10 secretion by normal and malignant B-1 cells. We found that inhibition of Src family kinases, spleen tyrosine kinase, Syk, or Bruton's tyrosine kinase reduces constitutive IL-10 production by both normal and malignant B-1 cells.
(© 2015 New York Academy of Sciences.)
Databáze: MEDLINE
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