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.