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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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
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

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

Cite this

Berkowska, M. A., Heeringa, J. J., Hajdarbegovic, E., Van Der Burg, M., Thio, H. B., Van Hagen, P. M., Boon, L., Orfao, A., Van Dongen, J. J. M., & Van Zelm, M. C. (2014). Human IgE+ B cells are derived from T cell-dependent and T cell-independent pathways. Journal of Allergy and Clinical Immunology, 134(3), 688-697.e. https://doi.org/10.1016/j.jaci.2014.03.036