Role Of Regulatory B Cells In The Pathogenesis Of Psoriasis

The research on immune regulation is of great importance in field ofimmunology. Regulatory B cells （Breg） play a very important role in immunebalance and homeostasis. Traditionally, people thought that B cells had the abilityof positive immune modulation in the immune system. However, accumulatingdata showed that B cells also had the ability of negative immune modulation. In1996, Janeway group firstly found that B cells had the inhibitory anilities inexperimental autoimmune encephalomyelitis （EAE）. In1997, for the first time,Bhan et al proposed the conception of―Regulatory B cells‖, which was resultedfrom the fact that B cells could inhibit the inflammation Induced by T cells inchronic colitis. Thereafter, researchers demonstrated that B cells have thefunction of negative immune modulation in the mouse models of severalautoimmunity diseases, inflammation diseases, allergy, tumor immunity andanti-infection immunity. In2008, Tedder group identified that the sub-populationof B cells had the ability of negative immune modulation by producing IL-10,was and those cells were called as B10cells and the phenotypes wereCD19⁺CD5⁺CD1d^hi.Studies also showed that there are B10cells in human.In2009, Blair et aldemonstrated that regulatory B cells existed in systemic lupus erythematosus （SLE） patients, and the phenotype was CD19⁺CD24^hiCD38^hi. The negativeimmune modulation of regulatory B cells in human is also dependent on theproduction of IL-10, which is the same as Breg in mice. In2010, Yohei Iwata etal got the similar discovery that regulatory B cells existed in patient ofautoimmune diseases, such as SLE, rheumatoid arthritis, primary Sj gren’ssyndrome, autoimmune vesiculobullous skin disease and multiple sclerosis. Theinhibitory immune modulation was dependent on the production of IL-10.The compelling evidence showed that psoriasis is a Th1/Th17cellsdominant autoimmune disease, and there are aberrant regulatory function inpsoriasis patient. The abnormality of the quantity and function CD4⁺CD25⁺Tregand the variation of IL-10expression have been observed in the pathogenesis ofpsoriasis. In mice, it is has been demonstrated that B cells could have effect onthe development and function of Treg. The negative immune modulation ofregulatory B cells is partly dependent on CD4⁺CD25⁺Treg. Based on the abovestudies, we hypothesized that the abnormality of the quantity and functionCD4⁺CD25⁺Treg might be induced by regulatory B cells in psoriasis patients.We investigated the number, phenotype, function of B10cells in psoriasis. Theresults are as the following:1. The analysis on the number of B10cells in psoriasis patients: Bloodsamples were collected, and PBMCs were separated for culture. CpG+CD40Land PIB （PMA, ionomycin and Brefeldin A Solution） were added for5h culturing,then the cells were collected and stained with CD19and IL-10and subjectedfor FCM analysis. We found that the number of IL-10⁺B cells in psoriaticperipheral blood decreased compared with the healthy control group.2. The analysis of number of B10-pro cells in psoriasis patients: Bloodsamples were collected, and PBMCs were separated for culture. CpG+CD40L and PIB （PMA, ionomycin and Brefeldin A Solution） were added for48hculturing, then the cells were collected and stained with CD19and IL-10andsubjected for FCM analysis. We found that the numberof IL-10⁺B cells inpsoriatic peripheral blood elevateded compared with the healthy control group,which means that the number of B10-pro increased.3. The analysis of differentiation abilities of B10cells in psoriatic patient.Under different groups of stimuli the ratios of pro-B10cells were detectedbetween psoriasis patients and healthy controls. We found that there was nodifference in the differentiation abilities of B10cells between psoriasis patientsand normal control.4. The analysis of number of B10-pro cells in psoriatic peripheral blood afterthe treatments. The PBMC were treated as describled above. We found that afterthe treatments number of B10-pro cells were less than that before the treatmentsand healthy controls.5. The analysis on the phenotype of B10cells in psoriasis patients: Bloodsamples were collected, and PBMCs were separated and subjected for CD19,CD38and CD24staining after culture with four groups of stimulis. Then the cellswere analyzed by FCM. We found that under PIB or CD40L and CpGstimulating, the IL-10-secreting B cells showed mainly CD24^hiCD38loworCD24^hiCD38-phenotype, and under the PIB+CD40L+CpG stimulating, the ratioof IL-10secreting cells increased and mainly with CD24^hiCD38^hiphenotype.6. The analysis on the function of B10cells in psoriatic patient. Bloodsamples were collected, and PBMCs were separated and subjected for CD19,CD38and CD24staining. Then the CD19⁺CD24^hiCD38^hiB cells were sorted byFCM. Meanwhile, other cells excluded CD19⁺CD24^hiCD38^hiB cells were alsocollected. We compared the culture with and without CD19⁺CD24^hiCD38^hiB cells in the24wells plate-coated with anti-CD3for72h. We stimulated thesecells with P+I for last6h and collected the supernatant, and IFN-γ and TNF-αwere detected by ELISA. We found that the healthy persons’ B10significantlyinhibited the lymphocytes’ production of TNF-α, but the psoriasis patients’ B10couldn’t.Conclusion: Our studies showed for the first time that the number andfunction of B10cells were abnormal in psoriasis patient,indicating that B10cellsmight play a negative regulatory role in the progress of psoriasia. More studiesare needed to further our understanding of the role and mechanism of B10cells inpsoriasis.