期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 11, 页码 3207-3217出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20170580
关键词
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资金
- National Institutes of Health [T32AR007108, DP3-DK097672, DP3-DK111802, R01AI071163, K08AI112993]
- Children's Guild Association Endowed Chair in Pediatric Immunology
- Benaroya Family Gift Fund
- American College of Rheumatology Research and Education Foundation Rheumatology Career Development K Supplement
- Arthritis National Research Foundation Eng Tan Scholar Award
- Novel Research Grant from the Lupus Research Alliance
- Arnold Lee Smith Endowed Professorship for Research Faculty Development
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 (T-FH) 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-gamma, consistent with the critical roles for B cell-intrinsic IFN-gamma 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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