CD52 is elevated on B cells of SLE patients and regulates B cell function
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy and SLE individuals which revealed upregulated C...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
04 February 2021
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| In: |
Frontiers in immunology
Year: 2021, Volume: 11, Pages: 1-17 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.626820 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fimmu.2020.626820 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2020.626820/full 
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| Author Notes: | Kartik Bhamidipati, John L. Silberstein, Yashaar Chaichian, Matthew C. Baker, Tobias V. Lanz, Amin Zia, Yusuf S. Rasheed, Jennifer R. Cochran and William H. Robinson |
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| 520 | |a Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy and SLE individuals which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity. | ||
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