Human IgE+ B cells are derived from T cell-dependent and T cell-independent pathways

Magdalena A. Berkowska, Jorn J. Heeringa, Enes Hajdarbegovic, Mirjam Van Der Burg, H. Bing Thio, P. Martin Van Hagen, Louis Boon, Alberto Orfao, Jacques J M Van Dongen, Menno C. Van Zelm

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87 Citations (Scopus)

Abstract

Background The prevalence of IgE-mediated diseases has been increasing worldwide, yet IgE-expressing B cells are poorly characterized, mainly because of their scarcity and low membrane IgE levels. Objective We sought to study the immunobiology of human IgE-expressing B cells in healthy subjects and patients with allergic disease. Methods We used a stepwise approach for flow cytometric detection and purification of human IgE-expressing B cells in control subjects, CD40 ligand-deficient patients, and patients with atopic dermatitis. Molecular analysis of replication histories, somatic hypermutation (SHM), and immunoglobulin class-switching was performed. Results Using multicolor flow cytometry, we reliably detected IgE-expressing plasma cells and 2 IgE-expressing memory B-cell subsets. These IgE-expressing cells showed molecular and phenotypic signs of antigen responses. The replication history and SHM levels of IgE+ plasma cells and CD27+IgE+ memory B cells fitted with a germinal center (GC)-dependent pathway, often through an IgG intermediate, as evidenced from Sγ remnants in Sμ-Sε switch regions. CD27-IgE+ cells showed limited proliferation and SHM and were present in CD40 ligand-deficient patients, indicating a GC-independent origin. Patients with atopic dermatitis had normal numbers of blood IgE+ plasma cells and CD27+IgE+ memory B cells but increased numbers of CD27-IgE+ memory B cells with high SHM loads compared with those seen in healthy control subjects and patients with psoriasis. Conclusions We delineated GC-dependent and GC-independent IgE+ B-cell responses in healthy subjects and indicated involvement of the GC-independent pathway in a human IgE-mediated disease. These findings provide new insights into the pathogenesis of IgE-mediated diseases and might contribute to accurate monitoring of IgE + B cells in patients with severe disease undergoing anti-IgE treatment.

Original languageEnglish
Pages (from-to)688-697.e
Number of pages16
JournalThe Journal of Allergy and Clinical Immunology
Volume134
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • atopic dermatitis
  • B cell
  • CD40 ligand
  • IgE
  • plasma cell

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