Introduction
Systemic lupus erythematosus (SLE), a major systemic autoimmune disorder, affects humans with genetic susceptibility in certain environmental conditions(1). Its pathogenetic mechanisms remain unclear. It is admitted that autoantibodies represent the main determinants of SLE’s pathological signs. Antibodies could harm self-tissues via complement-mediated inflammatory reactions, programmed cell death and immune-complexes associated injury. However, the exact role of antibodies in SLE remains unraveled(2).
Apoptosis is strictly controlled by cell surface proteins (e.g., Fas) and intracellular proto-oncogenes such as Bcl-2 and Bax family members(3). It has been demonstrated that the apoptosis signaling pathway is obviously disordered in SLE. Abnormal production of a large number of apoptotic signaling molecules, including TNF-related apoptosis inducing ligand (TRAIL), TNF-like weak inducer of apoptosis (TWEAK) and death ligand FasL (Fas ligand), leads to abnormal increase of apoptosis(4, 5). In addition, individuals with SLE have trouble clearing apoptotic cells. Cell death (programmed cell death, necrosis and NETosis [affecting neutrophils via NETs]), provides most of the self-dsDNA that induces immune reactions and causes autoimmune disorders(6).
Natural immunity enables the identification and elimination of injured and apoptotic cells. Meanwhile, it also performs the intricate regulation of inflammatory response and enhances immune tolerance. Natural IgM (nIgM) represents a critical part of innate immunity in humans, reacting with multiple epitopes found in self-and non-self antigens(7). Therefore, nIgM deficiency increases the tendency toward the development of autoimmune disorders; nIgM is indeed very important in clearing apoptotic cells and preventing them from triggering autoimmunity.
B-1- and innate-like B- (ILBs) cells constitute the main natural IgM producers. It is admitted that 80% of serum natural IgM is produced by B1 cells(8). On the other hand, ILBs represent a heterogeneous group of atypical B cells possessing innate sensing and responding features. Mouse ILBs comprise B1-, marginal zone (MZ) B- and other related B cells. CD19+CD27+IgD+B cells (or unswitched memory B cells) have been considered ILBs in humans(9). ILBs keep natural IgM amounts at the steady state, and quickly gain immune modulatory features via secretion of natural IgM and IL-10 after innate activation(10). Our previous study indicated CD27+IgD+B cell impairment in rheumatoid arthritis (RA), likely contributing to disease perpetuation(11). However, CD27+IgD+B cell properties and function in SLE remain undefined.
Here, we determined the amounts and natural antibody-like IgM-producing capacity of CD27+IgD+B cells in SLE patients. In addition, we analyzed their clinical associations and revealed their tendency after therapy.