Introduction
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune
disease that develops in genetically susceptible individuals in response
to environmental factors(1). The pathogenesis remains to be fully
elucidated.
Autoantibodies
are key
mediators
in determining the clinical manifestations of SLE. The mechanisms by
which antibodies may be harmful to self-tissues encompassed complement
mediated inflammation, cell
apoptosis
and
immune-complexes
mediated damage. However, the precise cooperation of antibodies in SLE
have not been unraveled so far(2).
Apoptosis is an energy-dependent
process that leads to the programmed destruction of cells. It is tightly
regulated by the expression of cell surface molecules such as Fas and
intracellular protooncogenes including Bcl-2 and the Bax family
members(3). It has been proved that apoptotic signaling pathway is
obviously disordered in SLE patients. Abnormal expression of a large
number of apoptotic signaling molecules such as TNF-related apoptosis
inducing ligand (TRAIL), TNF-like weak inducer of apoptosis (TWEAK) and
death ligand FasL (Fas ligand) leads to abnormal increase of apoptotic
cells(4, 5). In addition, the body of SLE patients also has obstacles to
the removal of apoptotic cells. Cell death, including apoptosis,
necrosis and NETosis (special cell death of neutrophil through NETs), is
the major potential resource of self-dsDNA which activates the immune
system and leads finally to autoimmune disease(6).
Natural immunity is responsible for identification and elimination of
damaged and apoptotic cells. Meanwhile, it also complete the intricate
regulation of inflammatory response and enhance immune
tolerance. Natural IgM(nIgM) is an
important component of the body’s innate immune system. nIgM is an
evolutionarily conserved molecule and reacts with a variety of epitopes
expressed on both self-and non-self antigens (7). nIgM deficiency is
associated with an increased tendency toward the development of
autoimmune disease. It plays a key role in the clearance of apoptotic
cells and prevents apoptotic cells from inducing abnormal autoimmunity.
B-1 cells and innate-like B cells
(ILBs) are proved to be the major producer of natural IgM. Early
transfer experiments showed that more than 80% of serum natural IgM is
derived from B1
cells(8).
ILBs are heterogeneous populations of unconventional B cells with innate
sensing and responding properties. In mice, ILBs are composed of B1
cells, marginal zone (MZ) B cells and other related B cells.
CD19+CD27+IgD+B cells which are also termed as un-switched memory B cells have been
proposed to be a kind of human ILBs(9). ILBs maintain natural IgM levels
at steady state, and they can rapidly acquire immune regulatory
activities through the secretion of natural IgM and IL-10 after innate
activation(10). Our previous study indicated that
CD27+IgD+B cells were impaired in
rheumatoid arthritis (RA) with dysfunctional features, which might
contribute to the disease perpetuation(11). Nevertheless, the
characteristics of CD27+IgD+ B cells
and their potential role in SLE are largely unknown.
In this study, we determined the frequencies and natural antibody-like
IgM-producing capacity of CD27+IgD+B
cells in SLE patients. In addition, we also analyzed their clinical
associations and revealed their tendency after therapy.