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Role of B cell receptor signaling in IL‐10 production by normal and malignant B‐1 cells
Author(s) -
Alhakeem Sara S.,
Sindhava Vishal J.,
McKenna Mary K.,
Gachuki Beth W.,
Byrd John C.,
Muthusamy Natarajan,
Bondada Subbarao
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12802
Subject(s) - syk , b cell receptor , b cell , b 1 cell , breakpoint cluster region , zap70 , bruton's tyrosine kinase , biology , cd5 , cancer research , microbiology and biotechnology , tyrosine kinase , regulatory b cells , signal transduction , receptor , immune system , immunology , antibody , antigen presenting cell , t cell , biochemistry
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.