Reduced memory B cells in patients with hyper IgE syndrome

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

“…Moreover, there are mutual immune responses between AR-HIES and AD-HIES patients, including diminished Th17 cells (P1, P2, P3, P7, P8 and P9) (Renner et al 2008) and decreased B-memory cells (P1, P2, P6, P7, P8, P9, and P11) although these failed to predict patients at highrisk of infection, consistent with a previous study (Speckmann et al 2008).…”

Functional STAT3 deficiency compromises the generation of human T follicular helper cells

“…26,30,31 Given the critical role of Tfh cells in humoral immune responses, it makes teleologic sense that this level of redundancy evolved to protect against the detrimental effects of Tfh cell deficiency. In contrast, use of STAT3 by several cytokines in the generation of human Tfh cells provides an explanation for why STAT3 MUT patients exhibit defects in humoral immune responses (including reductions in circulating CD4 ϩ CXCR5 ϩ CD45RA Ϫ and CD45RA ϩ Tfh-like cells, memory B cells and an inability to mount protective Ab responses after vaccination or natural infection 24,47,48 ) that cannot be compensated entirely by IL-12-dependent STAT4 signaling. These clinical, cellular, and serologic features of STAT3 deficiency are reminiscent of patients with mutations in ICOS and CD40LG, 49,50 which largely result from an absence of B-cell help by Tfh cells.…”

Therapeutic implications of advances in our understanding of transitional B-cell development in humans

“…Several loss-of-function or loss-of-expression mutations in genes that cause specific immune-deficient conditions impair the ability of the naive B cells to undergo Ig class-switching to become memory B cells or Ig-producing plasma cells, thereby compromising long-lived humoral immunity in the affected patients [6]. Patients with mutations in SH2D1A/SAP (which causes XLP [85,86]), CD40L, CD40 and NEMO (which cause hyper-IgM syndrome [87,88]), ICOS [89] or CD19 (which cause CVID) [90,91] or STAT3 (which causes autosomal dominant hyper-IgE syndrome [28,92]), all have reductions in memory B cells, particularly CD27 + IgM -IgD -classswitched B cells (Figure 1). These conditions present with normal/ increased levels of serum IgM but a deficiency in switched Ig isotypes and/or impaired antigen-specific antibody responses.…”