Abstract:
:Treatment of systemic lupus erythematosus patients with epratuzumab (Emab), a humanized monoclonal antibody targeting CD22, leads to moderately reduced B-cell numbers but does not completely deplete B cells. Emab appears to induce immunomodulation of B cells, but the exact mode of action has not been defined. In the present study, we aimed to understand the effects of Emab on B cells using a humanized mouse model (Huki CD22), in which the B cells express human instead of murine CD22. Emab administration to Huki CD22 mice results in rapid and long-lasting CD22 internalization. There was no influence on B-cell turnover, but B-cell apoptosis ex vivo was increased. Emab administration to Huki CD22 mice had no effect on B-cell numbers in several lymphatic organs, nor in blood. In vitro exposure of B cells from Huki CD22 mice to Emab resulted in decreased B-cell receptor (BCR) induced Ca(2+) mobilization, whereas B-cell proliferation after Toll-like receptor (TLR) stimulation was not affected. In addition, IL-10 production was slightly increased after TLR and anti-CD40 stimulation, whereas IL-6 production was unchanged. In conclusion, Emab appears to inhibit BCR signaling in a CD22-dependent fashion without strong influence on B-cell development and B-cell populations.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Özgör L,Brandl C,Shock A,Nitschke Ldoi
10.1002/eji.201646383subject
Has Abstractpub_date
2016-09-01 00:00:00pages
2260-72issue
9eissn
0014-2980issn
1521-4141journal_volume
46pub_type
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200001)30:1<87::AID-IMMU87>3.0.C
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journal_title:European journal of immunology
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pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090306
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:2014-01-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250336
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201141452
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830241131
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324511
更新日期:2004-03-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170621
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:1977-03-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200317
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250622
更新日期:1995-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830231213
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230143
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201444673
更新日期:2014-12-01 00:00:00
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journal_title:European journal of immunology
pub_type: 临床试验,杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260630
更新日期:1996-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830150814
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830160824
更新日期:1986-08-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200939514
更新日期:2009-08-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270433
更新日期:1997-04-01 00:00:00