Session Information
Title: B cell Biology and Targets in Autoimmune Disease: Systemic Lupus Erythematosus and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease associated with deposition of autoantibodies such as anti DNA antibody. After activation of B cells in lymphoid tissues, B cells circulate in the blood as “plasmablast” ,migrate to bone marrow and reside as plasma cells which produce antibodies. Specific targeting of circulating plasmablast might be a novel strategy for SLE treatment. Recently, CD19+CD38+CD43+ B cell subset from healthy control (HC) are reported to be “pre-plasmablast” phenotype based on gene expression profiling. The clarification of biological properties of CD19+CD38+CD43+ B cell subset in SLE patients might provide us a clue to specific targeting to this population. In this study, we analyzed the gene profiling of the circulating CD19+CD38+CD43+ B cells in HC and SLE using Agilent based microarray technologies.
Methods:
Naïve B cell (CD19+CD27–CD38–CD43–), memory B cell(CD19+CD27+CD38–CD43–) and CD19+CD38+CD43+ B cell were sorted with FACS AriaII from HC and SLE (n=4, respectively). Total RNA were isolated and labelled, then mRNA was analyzed with Aglinet microarray. Gene profiling data was analyzed with GeneSpring and Ingenuity Pathway Analysis software. Statistic analysis was performed by Fisher’s exact test in upregulator, canonical pathway and gene function analysis, and by modified t-test in comparative analysis between HC and SLE or each B cell subset.
Results:
Comparison of gene profiling of CD19+CD38+CD43+ B cell and naïve/memory B cell showed that genes differentially expressed in CD19+CD38+ CD43+ B cell were significantly regulated by several transcriptional factors which play roles in cell cycle and proliferation, such as E2F1, MYC E2F3 (p=4.47 x 10-19, 1.69 x 10-16, 3.73 x 10-9, respectively) in addition to XBP-1, PRDM and PAX5 which are well known to function in differentiation from B cell to plasma cells. In comparison of each B cell subset between HC and SLE patients, 2467 genes were significantly changed in CD19+CD38+CD43+ B cell. Among them, 1967 genes were changed only in CD19+CD38+CD43+ B cell and 123 genes were changed commonly in CD19+CD38+CD43+ B cell, naïve and memory B cell. Canonical pathway analysis showed that interferon signaling was significantly up-regulated in the commonly changed genes (p=1.35 x 10-6), in contrast, cell cycle related pathways, such as Role of BRCA1 in DNA Damage Response, Mismatch Repair in Eukaryotes and Cell Cycle Control of Chromosomal Replication were significantly increased (p=7.41 x 10-7, 3.09 x 10-6, 2.82 x 10-5, respectively) in only CD19+ CD38+ CD43+ B cell increased genes. 266 genes were cell cycle related genes among 1516 genes up-regulated in CD19+ CD38+ CD43+ B cell.
Conclusion:
Gene profiling analysis suggested that CD19+CD38+CD43+ B cell have more proliferating properties than naïve, memory B cell subsets and this population of SLE patients express more cell cycle related genes than HC.
Disclosure:
H. Fujii,
None;
T. Machiyama,
None;
K. Akita,
None;
Y. Kamogawa,
None;
R. Watanabe,
None;
Y. Fujita,
None;
Y. Shirota,
None;
S. Saito,
None;
T. Ishii,
None;
H. Harigae,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-cd19cd38cd43-b-cell-subset-in-sle-patients-have-more-cell-cycle-related-genes-than-healthy-controls/