Introduction: B cells perform various immunological functions that include Ab production, Ag presentation, secretion of multiple cytokines, and regulation of immune responses, mainly via secretion of IL-10. While the liver is regarded both as an important immune organ and a tolerogenic environment, little is known about the functional biology of hepatic B cells.

Methods: Male C57BL/6 (B6) mice were used for comparative phenotypic and functional analysis of liver and spleen B cells in the normal steady state and following their activation in vitro or in vivo in response to LPS stimulation. Flow cytometry was used to characterize cell surface markers and intracellular cytokine expression while cytokine secretion was quantified by Flex Set. In addition, to determine the influence of hepatic B cells on liver dendritic cells (DC), wild-type (WT) B6 mice and B-cell-deficient (ΜMT) mice were used as sources of DC for phenotypic and functional analyses.

Results: In response to in vivo LPS stimulation, normal mouse liver B cells rapidly increased their cell surface expression of CD39, CD80, and CD86, and produced significantly elevated levels of proinflammatory IFN-Γ, IL-6, and TNFΑ compared with secondary lymphoid tissue B cells. Moreover, unlike activated splenic B cells, which produced abundant IL-10, activated liver B cells secreted minimal IL-10. These data suggest that liver B cells can positively regulate hepatic inflammatory responses. Consistent with this, when compared with liver conventional DCs from B cell-deficient uMTmice, those from B cell-competent WT mice exhibited greater immuno-stimulatory function as evidenced by higher expression of the DC activation marker and co-stimulatory molecule CD86, greater production of pro-inflammatory IFN-Γ, IL-6, and IL-12p40, and less secretion of anti-inflammatory IL-10.

Conclusion: Liver B cells are well-equipped to promote hepatic inflammation, and to counteract the liver tolerogenic milieu to maintain the balance between immunity to pathogens and tolerance to dietary and other Ags in the liver.

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