Artikel
Filling of emptied survival niches with protective plasma cells in lupus prone BcN/LmoJ mice
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Autoren
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Laleh Khodadadi
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Qingyu Cheng
- Charité – Universitätsmedizin Berlin, Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Deutsches Rheuma-Forschungszentrum Berlin, Leibniz Institut, Berlin
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Adriano Taddeo
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Bimba Franziska Hoyer
- Sektion Rheumatologie/Zentrum für Entzündungsmedizin, Med. Klinik I, UKSH, Campus Kiel, Kiel
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Andreas Radbruch
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Falk Hiepe
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Immunoablation with antithymocyte globulin flollowed by autologous stem cell transplantation is able to deplete long-lived plasma cells in severe autoimmune disease such as SLE. However, there is a high risk of infections and development of secondary autoimmune disorders. Our aim is to improve the outcome by refill the emptied niches with adoptive transfer of protective plasmablasts after plasma cell depletion in lupus prone BcN/LmoJ mice.
Methods: CD138+ plasmablasts were isolated from donor mice by MACS sorting 5 days after boost of OVA immunization. Then, these cells were adoptively transferred into pretreated recipient mice with anti-CD20 and bortezomib to deplete B and plasma cells, respectively. We planned three different transfer groups: a) C57BL/6 to C57BL/6, b) BcN/LmoJ to BcN/LmoJ and c) C57BL/6 to BcN/LmoJ.
Results: IgG anti-OVA antibody produced by donor OVA-specific plasmablasts could be detected with high level in C57BL/6 recipient mice (group a) at 10 week after transfer, while it was undetectable in BcN/LmoJ recipient groups (b and c). Interestingly, transferred PCs labeled with CFSE could be detected in bone marrow of BcN/LmoJ recipient mice on day 5 but not later. Anti-dsDNA antibody level decreased transiently in BCN/LmoJ recipient groups.
Conclusion: Adoptively transferred plasmablasts can migrate to the bone marrow in both C57BL/6 and BcN/LmoJ mice but they cannot survive for long-term in BcN/LmoJ mice. There is a possibilty of high competition for survival niche in autoimmune model due to B cell hyperactivity. However, further investigation should be performed to draw a clear conclusion.
