MYSM1/miR-150/FLT3 inhibits B1a cell proliferation.

Xiao-Xia Jiang,Si-Yi Chen,Jing Zhang,Jianping Guo,Yaping Gao,Rong Mu,Hong Li,Fengjun Xiao,Beifen Shen,Bing Liu,Yan-Mei Yang,Changyong Wang,Yu Liu,Zhanguo Li,Guang Yang

doi:10.18632/oncotarget.11738

Abstract

The aberrant expansion of B1a cells has been observed in several murine autoimmune disease models; however, the mechanism of such proliferation of B1a cells is still limited. Here, we identify that Myb Like, SWIRM And MPN Domains 1 (MYSM1), a histone H2A deubiquitinase, plays an intrinsic role in the proliferation of B1a cells where MYSM1 deficiency results in the increased proliferation of B1a cells in mice. We demonstrate that MYSM1 recruits c-Myc to the promoter of miR-150 and stimulates the transcription of miR-150. Our further investigation shows that miR-150 decreases FMS-like tyrosine kinase 3 (FLT3) in B1a cells. In agreement with our animal studies, the percentage of FLT3+ B1 cells in Systemic Lupus Erythematosus (SLE) patients is significantly higher than healthy control. Thus, this study uncovers a novel pathway MYSM1/miR-150/FLT3 that inhibits proliferation of B1a, which may be involved in the pathogenesis of SLE.

Highlights

B1a cells are specialized B cells that constitute only a small fraction of the total B population, but are a significant source of serum antibodies
Due to the important role of B1a cells in innate immunity, we further explored the function of MYSM1 in B1a cell development
The total B cell frequency within the lymphocyte gate did not show much difference between the MYSM1−/− mice and their WT counterparts, while the proportion of B1a cells to total B cells was increased by a factor of 1.5 (Figure 1A, 1B), though the total number of B1a cells decreased in MYSM1−/− mice

Summary

Introduction

B1a cells are specialized B cells that constitute only a small fraction of the total B population, but are a significant source of serum antibodies. The natural antibodies of B1a cells play a crucial role in the first-line defense against microbial infections in mice, acting before an adaptive immune response by conventional B2 cells [5,6,7]. In contrast to conventional B cells (B2 cells), most long-lived B1a cells are thought to be derived from precursors in fetal liver rather than from adult bone marrow. Despite their positive role in first-line antimicrobial defense, elevated B1a cell numbers is often associated with autoimmunity [8]. The mechanism of abnormal B1a cell proliferation is far from clear

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Conclusion