Antibodies from Donor B Cells Are Not Required for Initiating but Required for Persisting Scleroderma in Chronic Gvhd
| Autor: | Xiong Ni, Defu Zeng, Hua Jin, Qifa Liu, Ruishu Deng, James S. Young, Heather F. Johnston |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Blood. 124:3817-3817 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v124.21.3817.3817 |
| Popis: | We recently reported that in a chronic graft versus host disease (GVHD) model of DBA/2 donor to MHC-matched BALB/c recipient, donor CD4+ T and B cell interaction resulted in not only hyperglobulinemia and glomerulonephritis but also scleroderma (J. Immunol. 2012). It is well known that glomerulonephritis is caused by immune complex deposition. However, the role of antibodies from donor B cells in the pathogenesis of scleroderma remains unclear. To address this question, we generated DBA/2 mice whose B cells have APC function but cannot secrete antibodies by backcrossing IgHµg1 mice from Dr. Rajewsky’s lab (JEM 2007). We observed that, while transplanting T-cell-depleted bone marrow (TCD-BM) and spleen cells from littermate control mice induced proteinuria and scleroderma, transplanting BM and spleen cells from IgHµg1 DBA/2 mice induced no proteinuria, but the recipients developed scleroderma ~35 days after HCT. Interestingly, the scleroderma gradually recovered ~55 days after HCT. 40 days after HCT, scleroderma recipients transplanted with WT spleen cells (Rec-WT) or recipients transplanted with IgHµg1 spleen cells (Rec-IgHµg1) both had high percentage (~12%) of IFN-g+ or IL-17+ CD4+ T cells in the peripheral lymph node (PLN) and skin tissues, as compared to that (~3%) of GVHD-free recipients given TCD-BM alone (Rec-TCD). While Rec-WT had severe reduction of CD4+CD8+ thymocytes, the Rec-IgHµg1 had no reduction of the thymocytes, as compared to that of Rec-TCD. By day 60 after HCT, the Rec-WT with ongoing scleroderma still had ~10% IFN-g+ or IL-17+ CD4+ T cells in the PLN and skin tissues; in contrast, although the Rec-IgHµg1 with reversal of scleroderma still had >10% IFN-g+or IL-17+ CD4+ T cells in the PLN, those cells in the skin had reduced to Disclosures No relevant conflicts of interest to declare. |
| Databáze: | OpenAIRE |
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