Congenital T cell activation blocks transitional to follicular B cell maturation in humans. Congenital T cell activation blocks transitional to follicular B cell maturation in humans

In patients with CTLA4 deficiency, CD40L-expressing T cells inhibit transitional to follicular B cell maturation in the T cell zone of lymph nodes through the induction of mTORC1 signaling in transitional B cells. We apply scRNA-seq to identify upregulation of PI3K, mTORC1, and oxidative phosphorylation pathways in patients with CTLA4 deficiency, and to characterize resolution of follicular block after treatment with abatacept. Overall design: scRNA-seq of transitional B cells from healthy donors and patients with CTLA4 deficiency; one set of pre- and post-abatacept treatment from the same CTLA4-deficient patient.