Discussion
In this study, we observed that the rate of CD27+IgD+B cells were decreased and functionally impaired in producing natural antibody-like IgM in patients with SLE when compared with healthy controls. The number of CD27+IgD+B cells is correlated with the clinical characteristics of SLE patients. After effective therapy, these CD27+IgD+B cells could get recovered.
In SLE, the number of apoptotic cells increases while the phagocytosis function is impaired (14, 15). The contemporaneous occurrence of enhanced apoptosis and impaired phagocytosis is considered to be a key process in the pathogenesis of SLE and can lead to the cumulative exposure to the autoantigens which resulted in autoantibody production and autoimmunity(16). Apoptotic cells are normally phagocytosed by professional phagocytes such as macrophages, but the clearance of apoptotic cells depends not only on functioning phagocytes but also on soluble proteins that act as opsonins and/or bridging molecules. Phagocytosis of apoptotic cells can be enhanced by C-reactive protein (CRP), serum amyloid P component (SAP), C1q, IgM, MBL and other proteins, forming a redundant backup mechanism. Previous studies have found that phagocytic activity of macrophages is reduced three-fold to four-fold in the absence of IgM (17). Decreased natural IgM level in SLE patients may lead to inefficient clearance of apoptotic cells, leading to the accumulation of dead cells in peripheral blood(18). SLE patients were reported to demonstrate lower levels of anti-PC natural IgM, reductions of which correlated with duration of the disease. Lower levels of anti-PC natural IgM were also reported to be associated with more frequent cardiovascular events in patients with SLE (19). However, till now little is known about the causes of natural IgM defects in SLE patients.
In our previous study, we proved that CD27+IgD+B cells can spontaneously secrete
IgM that were polyreactive and low affinitive. We termed these CD27+IgD+B cells-derived IgM as natural antibody-like IgM. In this study, we found that CD27+IgD+B cells in SLE patients were significantly reduced and negatively correlated with SLEDAI and anti-dsDNA autoantibodies. These data are consistent with previous reports (20, 21) and, taken together, indicate that the B cell-subsets are disordered in SLE patients. Since different B cell subsets have different functional characteristics, the imbalance of their proportions will lead to the imbalance of immune homeostasis and promote the development of the disease to some extent. Cytokines such as IFN-gamma, BAFF, TNF-alpha, il-6, il-21 in the serum of SLE patients will affect the B cell signaling pathway and thus increase its activation and differentiation(22-24). Therefore, we speculated that the inflammatory environment in SLE patients is one of the reasons for the reduction of CD27+IgD+B cells, but this speculation need to be further studied.
In addition, QPCR and ELISPOT analyses showed that the ability of CD27+IgD+B cells to secrete IgM in SLE patients was significantly lower than that in healthy control, indicating that in SLE patients, CD27+IgD+B cells has defects not only in quantity, but also in function. Therefore, this is also a reason for the accumulation of apoptotic cells and the generation of autoimmunity in SLE patients. The decreased TCR or BCR diversity has been observed in cancers and autoimmune diseases, which may contribute to the development of the diseases(25). Our previous research has shown that the BCR repertoire of CD27+IgD+B cells was altered in RA. Compared with healthy controls, the variable region of the CD27+IgD+B cells-derived IgM μ chain showed much narrower spectrum. Therefore, we speculated that the BCR repertoire of CD27+IgD+B cells was also changed in SLE, and the following study will be conducted to score the BCR repertoire of CD27+IgD+B cells in SLE patients.
In summary, we demonstrated that CD27+IgD+B cells were numerically and functionally impaired in SLE. CD27+IgD+B cells are a reliable biomarker for active SLE and that the role of these cells in the pathogenesis of SLE deserve to further investigation.