Autoreactive B cells play an important role in SLE
B cells are regarded to play a central role in the adaptive immune
response. It was believed that autoreactive B cells in SLE were able to
further differentiate into abnormal plasma cells secreting
autoantibodies after their activation by self-antigen and autoreactive T
cells 30, 53-55. Immature B cells originate from stem
cells in bone marrow; their diversity among BCR specificities is
generated by the random rearrangement of gene segments during early
B-cell development 56, 57. After experiencing positive
selection, pro-B and pre-B cells have been shown to both express mIgM
and become immature B cells 56, 58. Autoreactive
immature B cells suffer from apoptosis and are deleted during negative
selection 56, 57. Although the mechanism through which
autoreactive B cells pass through negative selection remains unclear,
some researchers believe that Fas signaling is involved in the apoptosis
of autoreactive B cells 59 and that peripheral B cells
may be activated by foreign antigens. Fas-deficiency has been shown to
possibly result in the failure of autoreactive B cells to undergo
apoptosis in an SLE murine model 59, 60. Then, MHC-II,
when present with self-antigens in activated autoreactive B cells, may
interact with autoreactive CD4+ T cells and activate autoreactive T
cells 7, 30. Autoreactive B cells differentiate into
plasma cells secreting autoantibodies with the help of autoreactive CD4+
T cells. Furthermore, the production of autoantibody has been reported
to be independent of CD4+ T cells 7, 14, 30.