Background Pre-naive B cells are a unique developmental intermediate in human B cell development at developmental stage between transitional and naive B cells. Although immature, pre-naïve B cells were shown to have functions of mature B cells, but their role in immune response is unknown.
Objectives The aim of our study was to determine the functional role of pre-naive B cells in immune responses.
Methods Peripheral blood CD27–CD38Int pre-naïve B cells, CD27–CD38lo naïve B cells, and CD27+ memory B cells from healthy individuals and systemic lupus erythematosus (SLE) patients were sorted and stimulated with CD154-L cells. Activated B cells were analyzed for IL-10 and accessory molecule expression, and after co-cultured with sorted CD4+CD25– T cells, T cell proliferation and cytokine production was measured. After inducing B cells to differentiate into plasma cells, culture supernatant was tested for reactivity of IgM antibodies to ssDNA, dsDNA and histone. Transitional, pre-naïve and naïve B cell were analyzed for IgH CDR3 length and positive charged amino acids.
Results CD40-stimulated pre-naïve B cells produce high amounts of IL-10. CD40 activated pre-naïve B cells did not suppress CD4+ T cell cytokine production, but demonstrated IL-10 mediated ineffective stimulation of CD4+ T cell proliferation. Pre-naive B cells also showed impaired expression of co-stimulatory molecules after CD40 engagement. However, IL-10 is not involved in the differentiation of pre-naive B cells into plasma cells, and IgM antibodies produced by pre-naïve B cells were reactive to ssDNA. SLE pre-naïve B cells were defective in producing IL-10 upon receiving CD40 signal, and costimulatory molecule expression after CD40 engagement was not impaired.
Conclusions Our data suggest that there is an inherent and IL-10 mediated mechanism that limits the capacity of activated pre-naïve B cells from participating in cellular immune response, but these cells can participate in humoral immune response by production of auto-Abs. Defects in pre-naïve B cell function may result in break in self-tolerance, and could enhance the development of autoimmunity.
Acknowledgements This work was supported by Basic Science Research Program through the National Research Foundation (NRF) funded by the ministry of Education and Technology (2010-0010589).
Disclosure of Interest None declared