CD23 expression on switched memory B cells bridges T‐B cell interaction in allergic rhinitis

Abstract

Background: The contribution of B-cell subsets and T-B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This study aimed to outline circulating B-cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR. Methods: IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigenspecific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co-cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B-cell subsets and clinical benefits of AIT were analyzed. Results: Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19 + CD20 + CD27 + IgD − switched memory B cells was significantly enhanced and positively correlated with antigen-specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL-4, which was unable to be sufficiently suppressed by AR-associated Tfr cells with defective IL-10 expression.

Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

“…These cells were able to restrain class switching to IgE, but not IgG, via IL‐10 in vitro 86 . In addition, cT FR cells derived from patients with AR had a compromised IL‐10‐producing capacity relative to those obtained from healthy subjects 87 …”

“…Using unsupervised hierarchical clustering and correlation analysis, additional negative correlations have been identified in the cT FR cell frequencies, with symptom scores and allergen‐specific IgE levels in patients with AR 35,87 . Notably, cT FR /cT FH 2 cell ratios show a better correlation with symptom severity than the frequencies of T FR cells ( r = −.516 for cT FR /cT FH 2 cell ratio vs r = −.427 for T FR cells), 35,87 emphasizing the importance of T FH and T FR cell balances in the pathogenesis of AR.…”

“…The induction of allergen‐specific IgG4 has been associated with successful AIT 34 . Yao et al 87 showed that the increase of Der p‐specific IgG4 levels positively correlated with the reduction of Der p‐specific IgE levels in patients with AR undergoing subcutaneous AIT. These data raised a notion that AIT may induce a shift from allergen‐specific IgE to IgG4, which is potentially mediated by IL‐10‐secreting T FR cells 84 .…”

“…Consistently, patients with CTLA‐4 haploinsufficiency displayed higher frequencies of cT FH cells with concomitantly lower frequencies of cT FR cells than healthy subjects 83 . Although several studies have shown that T FR cell‐derived IL‐10 promoted GC responses and IgE production in mice, 84,85 IL‐10‐producing follicular T cells appear to inhibit IgE production in humans 86,87 . Despite these progresses, the molecular mechanisms underlying the suppressive function of T FR cells requires further investigation, particularly in comparison to conventional T REG cells.…”

Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity

“…It was reported that the expression of CD23 was enhanced on CD19 + CD20 + CD27 + IgD − switching memory B cells and positively correlated with antigen‐specific IgE levels and the T FH 2 cell ratio in AR patients. T FH 2 cells have the capacity to promote CD23 expression on switching memory B cells by secreting the cytokine IL‐4 122 …”