B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity.
B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity.
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DOI：
10.1084/jem.20170580
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Jackson SW
中科院分区：
文献类型：
--
作者：
Arkatkar T;Du SW;Jacobs HM;Dam EM;Hou B;Buckner JH;Rawlings DJ;Jackson SW
Arkatkar et al. report that B cell–derived IL-6 is critical for T follicular helper cell differentiation, spontaneous germinal center formation, and class-switched autoantibody production during humoral autoimmunity. Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.
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影响因子：
27.4
作者：
Munroe ME;Lu R;Zhao YD;Fife DA;Robertson JM;Guthridge JM;Niewold TB;Tsokos GC;Keith MP;Harley JB;James JA
通讯作者：
James JA
影响因子：
32.4
作者：
Hou B;Saudan P;Ott G;Wheeler ML;Ji M;Kuzmich L;Lee LM;Coffman RL;Bachmann MF;DeFranco AL
通讯作者：
DeFranco AL
DOI：
10.4049/jimmunol.0904023
发表时间：
2010-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Poholek AC;Hansen K;Hernandez SG;Eto D;Chandele A;Weinstein JS;Dong X;Odegard JM;Kaech SM;Dent AL;Crotty S;Craft J
通讯作者：
Craft J
DOI：
10.1084/jem.20151724
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jackson SW;Jacobs HM;Arkatkar T;Dam EM;Scharping NE;Kolhatkar NS;Hou B;Buckner JH;Rawlings DJ
通讯作者：
Rawlings DJ
DOI：
10.4049/jimmunol.1400098
发表时间：
2014-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jackson SW;Scharping NE;Kolhatkar NS;Khim S;Schwartz MA;Li QZ;Hudkins KL;Alpers CE;Liggitt D;Rawlings DJ
通讯作者：
Rawlings DJ