title: Role of B cell receptor signaling in IL-10 production by normal and malignant B-1 cells.
abstract: 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.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Alhakeem
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Vishal J
authors.initials: VJ
authors.lastname: Sindhava
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Mary K
authors.initials: MK
authors.lastname: McKenna
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Beth W
authors.initials: BW
authors.lastname: Gachuki
authors.affiliation: Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Subbarao
authors.initials: S
authors.lastname: Bondada
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000096:biosynthesis*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C556062:IL10 protein, mouse; D011947:Receptors, Antigen, B-Cell; D016753:Interleukin-10
keywords: B cell receptor; B-1 cell; IL-10; Toll-like receptor; chronic lymphocytic leukemia