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PMID: 26725861 Published · ppublish jpn

[The importance of B cell-T cell interaction in autoimmune diseases].

Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology ·Vol. 38 ·No. 5 ·2016-09-01

Iwata Shigeru, Tanaka Yoshiya

Abstract

B cells play a pivotal role in the pathogenesis of autoimmune diseases. In addition, B cells require interaction with helper CD4+ T cells to become activated. We assessed change of gene regulatory network that controls B cell differentiation after stimulation with BCR cross-linking, sCD40L, Toll-like Receptor (TLR) and cytokines such as IL-4/IL-21 in vitro. We found that combination with BCR, CD40 and TLR9 or IL-4/IL-21 signal via tyrosine kinases such as Syk/Btk/JAK caused robust gene expression of AICDA, BCL6, XBP1 and IgG production. We found that levels of Syk/Btk phosphorylation in B cells were preferentially higher in RA and SLE patients compared to healthy subjects. RA patients with higher p-Syk levels were significantly correlated to strongly positive for anti-citrullinated protein antibodies (ACPAs). Treatment with abatacept significantly reduced the levels of p-Syk in RA peripheral blood B cells, and also reduced the proportion of follicular helper T (Tfh) cells. We highlight tyrosine kinase such as Syk/Btk/JAK as potential targets for inhibiting B cell-T cell interactions in autoimmune diseases such as RA and SLE. We also state recent evidence of these drugs.

Article Info
Journal
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
Abbr.
Nihon Rinsho Meneki Gakkai Kaishi
ISSN
1349-7413
Published
2016-09-01
Indexed
2016-01-04
Updated
2016-11-26
Language
jpn
Country/Region
Japan
NLM ID
9505992
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