Background/Purpose: Pre-naive B cells represent an intermediate stage in human B cell development with some functions of mature cells, but their involvement in immune responses is unknown. The aim of this study was to determine the functional role of normal pre-naive B cells and possible abnormalities in systemic lupus erythematosus (SLE) that might contribute to disease pathogenesis.

Methods: Pre-naïve, naïve and memory B cells from healthy individuals and SLE patients were stimulated through CD40 and were analyzed for IL-10 production and co-stimulatory molecule expression, and their regulation of T cell activation. Autoreactivity of antibodies produced by pre-naïve B cells was tested by measuring IgM autoantibodies in culture supernatants after differentiation.

Results: CD40-stimulated pre-naive B cells produce large amounts of IL-10, but did not suppress CD4⁺ T cell cytokine production. Activated pre-naive B cells demonstrated IL-10 mediated ineffective promotion of CD4⁺ T cell activation, and IL-10 independent impairment of co-stimulatory molecule expression and TNF-a and IL-6 production. IgM antibodies produced by differentiated pre-naive B cells were reactive to ssDNA. SLE pre-naive B cells were defective in producing IL-10, and co-stimulatory molecule expression was enhanced, resulting in promotion of robust CD4⁺T cell activation.

Conclusion: There is an inherent and IL-10 mediated mechanism that limits the capacity of normal pre-naïve B cells from participating in cellular immune response, but these cells can differentiate into autoantibody secreting plasma cells. In SLE, defects in IL-10 secretion permit pre-naive B cells to promote CD4⁺ T cell activation, and may, thereby, enhance the development of autoimmunity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoregulatory-function-of-il-10-producing-pre-naive-b-cells-is-defective-in-systemic-lupus-erythematosus/