Figure 3.
CD21loB cells in IEIs. (A) CD21loCD19hi B cells were quantified in HDs (n = 94), as well as patients with the indicated IEI. The dashed line (-----) represents the mean of CD21loCD19hi B cells in HDs; the dotted lines (……) represent 1 standard error of the mean. AD: autosomal dominant; AR: autosomal recessive; XL: X-linked. Data for AR TBX21 deficiency are derived from a single patient but from multiple blood samples. Only one patient was available to test for AR JAK1 and AR STAT1 deficiency. For all other IEIs, multiple patients were tested. These data have previously been published in studies from the Tangye lab (16, 17, 18, 19, 20). (B) Scheme of differentiation of naïve B cells into CD21loT-bet+ B cells. Integration of signals through the BCR in combination with CD40 or TLRs induces expression of T-bet in B cells. T-bet expression is further increased following exposure to cytokines, such as IFNγ, IL-27, or IL-21 (possibly other cytokines, “x”). Cytokine-induced T-bet upregulation is required for further maturation of T-bet+ B cells, evidenced by acquisition of canonical surface receptors such as CXCR3, FCRL4/5, and CD11c. This second phase of CD21loT-bet+ B cell generation is abolished by T-bet deficiency (19). Refer to the image caption for details. Panel A: A vertical bar graph quantifying C D 21 l o C D 19 h i B cells in healthy donors and patients with various inborn errors of immunity. The x-axis lists different conditions, including healthy donors (H D), A R T B X 21 deficiency, X L C D 40 L deficiency, A R I L 21 R deficiency, A D I F N G R 1 deficiency, A R I L 27 R deficiency, A R J A K 1 deficiency, A R S T A T 1 deficiency, A D S T A T 1 deficiency, A D S T A T 3 deficiency, A R I R A K 4 deficiency, and A R C D 4 deficiency. The y-axis represents the percentage of B cells, ranging from 0 to 6 percent. The dashed line indicates the mean percentage of C D 21 l o C D 19 h i B cells in healthy donors, while the dotted lines represent one standard error of the mean. Each bar represents the mean value for each condition, with individual data points shown as black dots. Panel B: A diagram illustrating the progressive differentiation of naive B cells into C D 21 l o T-bet positive B cells. The diagram shows interactions between C D 4 positive T cells and naive B cells, involving signals such as T C R, C D 40 L and C D 40, and T L R s, leading to the induction of T B X 21 and expression of T-bet. Further exposure to cytokines like I F N gamma, I L 27, and I L 21 enhances T-bet expression, resulting in maturation into C D 21 l o T-bet positive B cells expressing receptors such as Z E B 2, C X C R 3, F C R L 5, and C D 11 c. T-bet deficiency is shown to impair this maturation process.

CD21 lo B cells in IEIs. (A) CD21loCD19hi B cells were quantified in HDs (n = 94), as well as patients with the indicated IEI. The dashed line (-----) represents the mean of CD21loCD19hi B cells in HDs; the dotted lines (……) represent 1 standard error of the mean. AD: autosomal dominant; AR: autosomal recessive; XL: X-linked. Data for AR TBX21 deficiency are derived from a single patient but from multiple blood samples. Only one patient was available to test for AR JAK1 and AR STAT1 deficiency. For all other IEIs, multiple patients were tested. These data have previously been published in studies from the Tangye lab (16, 17, 18, 19, 20). (B) Scheme of differentiation of naïve B cells into CD21loT-bet+ B cells. Integration of signals through the BCR in combination with CD40 or TLRs induces expression of T-bet in B cells. T-bet expression is further increased following exposure to cytokines, such as IFNγ, IL-27, or IL-21 (possibly other cytokines, “x”). Cytokine-induced T-bet upregulation is required for further maturation of T-bet+ B cells, evidenced by acquisition of canonical surface receptors such as CXCR3, FCRL4/5, and CD11c. This second phase of CD21loT-bet+ B cell generation is abolished by T-bet deficiency (19).

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal