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.