THU0044 SINGLE CELL ANALYSIS OF BONE MARROW AND PERIPHERAL ALTERED B CELL DIFFERENTIATION IN PATIENTS WITH ACTIVE SLE AND THE MECHANISM OF ABNORMAL EARLY B CELL DEVELOPMENT
Authors: T. Fu, Y. Yang, X. Gu, C. Dong, R. Zhao, J. Ji, X. Zhang, Z. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: B cell differentiation and dysfunction play a key role in the pathogenesis of Systemic lupus erythematosus (SLE). Bone marrow (BM) is the development organ of B cells, and also the home and residence place of plasma cells and memory B cells. However, there is a lack of studies on B cells in BM with lupus. Objectives: To map the development of BM and peripheral B cells and investigate the mechanism of abnormal early B cell development in SLE. Methods: A total of 11 SLE patients and 5 age- and sex-matched controls were recruited.BM and peripheral B cell subsets were measured by flow cytometry. sorting-purified B cell subsets were subject toSingle-cell RNA sequencing (scRNA-seq) and functional studies. Plasma cytokines and secreted immunoglobulins were detected by Luminex or ELISA. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI). Results: In the present study, we find out that the percentage of monocytes in MNC (p=0.070) and plasma cells(p=0.001)in CD19+ were significantly decreased in BM of SLE, compared to healthy controls. While, SLE patients had increased T%MNC(p=0.008) and B%CD19+(p=0.002) in BM that controls. In detail, the B cell subsets of bone marrow in patients with active lupus (SLEDAI≥8 score) were seriously disordered, showing the increasing T%MNC(p=0.049), propre-B%CD19+ (p=0.006)and immature B cell%CD19+ (p=0.010) than healthy donors. propre-B%CD19+ exhibited good relationship with SLEDAI. By integrating single B cell expression profiling and repertoire analysis, we map the development of B cells in BM and peripheral and pathogenic characteristics of early B cells, especially propre-B. Conclusion: These findings demonstrated that early B cells in BM, especially propre-B are abnormally differentiated with dysregulations. BM is an important organ targeted by SLE. This studyis not only to clarify the internal mechanism of the disorder of differentiation of B cells, but also to provide new clues for the targeted diagnosis and treatment of SLE. References: [1]Palanichamy, A., et al., Neutrophil-mediated IFN activation in the bone marrow alters B cell development in human and murine systemic lupus erythematosus. J Immunol, 2014. 192 (3): p. 906-18. [2]Papadaki, H.A., J.C. Marsh, and G.D. Eliopoulos, Bone marrow stem cells and stromal cells in autoimmune cytopenias. Leuk Lymphoma, 2002. 43 (4): p. 753-60. [3]Karrar, S. and D.S. Cunninghame Graham, Abnormal B Cell Development in Systemic Lupus Erythematosus: What the Genetics Tell Us. Arthritis Rheumatol, 2018. 70 (4): p. 496-507. [4]Woods, M., Y.R. Zou, and A. Davidson, Defects in Germinal Center Selection in SLE. Front Immunol, 2015. 6 : p. 425. [5] Upregulation of p16INK4A promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients. Cell Signal, 2012. 24 (12): p. 2307-14. Disclosure of Interests: None declared