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

Sara S. Alhakeem, Vishal J. Sindhava, Mary K. Mckenna, Beth W. Gachuki, John C. Byrd, Natarajan Muthusamy, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish
Pages (from-to)239-249
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1362
Issue number1
DOIs
StatePublished - Dec 1 2015

Bibliographical note

Publisher Copyright:
© 2015 The New York Academy of Sciences.

Keywords

  • B cell receptor
  • B-1 cell
  • Chronic lymphocytic leukemia
  • IL-10
  • Toll-like receptor

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • History and Philosophy of Science

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