Our findings report the first phenotypic characterization of Tfh and Tfr in human CD40 deficiency and describe differences to other HIGM syndromes caused by mutations in CD40L and AICDA. The single patient with CD40 deficiency analyzed, showed a marked reduction in circulating Tfh and Tfr cells suggesting that lack of CD40 signals contribute to an early demise of GCs in humans, similarly to mice (24). Here, CD40 is linked to hyperinsulinemic hypoglycemia, familial, 4.