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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.
Document Type
Article
Publication Date
12-1-2015
Digital Object Identifier (DOI)
doi: 10.1111/nyas.12802. Epub 2015 Jun 11
Repository Citation
Alhakeem, Sara S; Sindhava, Vishal J; McKenna, Mary K; Gachuki, Beth W; Byrd, John C; Muthusamy, Natarajan; and Bondada, Subbarao, "Role of B cell receptor signaling in IL-10 production by normal and malignant B-1 cells." (2015). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 156.
https://uknowledge.uky.edu/microbio_facpub/156
