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B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19⁺CD24^hiCD38^hi subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19⁺CD24^hiCD38^hi in the peripheral compartment of nonsplenectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19⁺ subpopulations (P < .03), and inhibition of monocyte TNF-α expression by activated B cells was reduced in patients with platelet numbers of < 50 × 10⁹ cells/L (P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were …