10.3389/fimmu.2019.02136.s010
Sarah Y. Weißenberg
Sarah Y.
Weißenberg
Franziska Szelinski
Franziska
Szelinski
Eva Schrezenmeier
Eva
Schrezenmeier
Ana-Luisa Stefanski
Ana-Luisa
Stefanski
Annika Wiedemann
Annika
Wiedemann
Hector Rincon-Arevalo
Hector
Rincon-Arevalo
Anna Welle
Anna
Welle
Annemarie Jungmann
Annemarie
Jungmann
Karl Nordström
Karl
Nordström
Jörn Walter
Jörn
Walter
Juliana Imgenberg-Kreuz
Juliana
Imgenberg-Kreuz
Gunnel Nordmark
Gunnel
Nordmark
Lars Rönnblom
Lars
Rönnblom
Prathyusha Bachali
Prathyusha
Bachali
Michelle D. Catalina
Michelle D.
Catalina
Amrie C. Grammer
Amrie C.
Grammer
Peter E. Lipsky
Peter E.
Lipsky
Andreia C. Lino
Andreia C.
Lino
Thomas Dörner
Thomas
Dörner
Table_4_Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.DOCX
Frontiers
2019
systemic lupus erythematosus
rheumatoid arthritis
primary Sjögren's syndrome
B cell receptor signaling
toll-like receptor 9
CD40
post-activation
anergy
2019-09-24 04:18:44
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_4_Identification_and_Characterization_of_Post-activated_B_Cells_in_Systemic_Autoimmune_Diseases_DOCX/9895265
<p>Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27<sup>−</sup> B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40–CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy.</p>