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IRF4 Deficiency Leads to Altered BCR Signalling Revealed by Enhanced PI3K Pathway, Decreased SHIP Expression and Defected Cytoskeletal Responses
Author(s) -
Budzyńska P. M.,
Niemelä M.,
Sarapulov A.V.,
Kyläniemi M.K.,
Nera K.P.,
Junttila S.,
Laiho A.,
Mattila P.K.,
Alinikula J.,
Lassila O.
Publication year - 2015
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12343
Subject(s) - signalling , microbiology and biotechnology , cytoskeleton , breakpoint cluster region , signalling pathways , pi3k/akt/mtor pathway , hedgehog signaling pathway , expression (computer science) , biology , signal transduction , genetics , receptor , cell , computer science , programming language
The graded expression of transcription factor interferon regulatory factor 4 ( IRF 4) regulates B cell development and is critical for plasma cell differentiation. However, the mechanisms, by which IRF 4 elicits its crucial tasks, are largely unknown. To characterize the molecular targets of IRF 4 in B cells, we established an IRF 4‐deficient DT 40 B cell line. We found that in the absence of IRF 4, the expression of several molecules involved in BCR signalling was altered. For example, the expression of B cell adaptor for PI3K ( BCAP ) was upregulated, whereas the SHIP (SH2‐containing Inositol 5?‐Phosphatase) expression was downregulated. These molecular unbalances were accompanied by increased BCR ‐induced calcium signalling, attenuated B cell linker protein ( BLNK ) and ERK activity and enhanced activity of PI3K/protein kinase B (Akt) pathway. Further, the IRF 4‐deficient cells showed dramatically diminished cytoskeletal responses to anti‐IgM cross‐linking. Our results show that IRF 4 has an important role in the regulation of BCR signalling and help to shed light on the molecular mechanisms of B cell development and germinal centre response.