Intrinsic properties of germinal center-derived B cells promote their enhanced class switching to IgE.

Abstract

BACKGROUND:

Research on the origins and development of human IgE-expressing (IgE(+) ) cells is required for understanding the pathogenesis of allergy and asthma. These studies have been thwarted by the rarity of IgE(+) cells in vivo and the low frequency of class switch recombination (CSR) to IgE ex vivo. To determine the main source of IgE(+) cells, we investigated the relation between the phenotypic composition of tonsil B cells and the CSR to IgE ex vivo.

METHODS:

Human tonsil B cells were analyzed by flow cytometry (FACS) and cultured with IL-4 and anti-CD40 to induce CSR to IgE. Naïve, germinal center (GC), early GC (eGC), and memory tonsil B cells were isolated by FACS, and their capacities for IL-4 and anti-CD40 signaling, cell proliferation, and de novo class switching to IgE were analyzed by RT-PCR and FACS.

RESULTS:

B cells from different tonsils exhibited varying capacities for CSR to IgE ex vivo. This was correlated with the percentage of eGC B cells in the tonsil at the outset of the culture. Despite relatively poor cell viability, eGC and GC B-cell cultures produced the highest yields of IgE(+) cells compared to naïve and memory B-cell cultures. The main factors accounting for this result were the strength of IL-4R and CD40 signaling and relative rates of cell proliferation.

CONCLUSIONS:

This study shows that the maturation state of tonsil B cells determines their capacity to undergo class switching to IgE ex vivo, with the GC-derived B cells yielding the highest percentage of IgE(+) cells.

• Authors: F Ramadani, N Upton, P Hobson, Y-C Chan, D Mzinza, H Bowen, C Kerridge, B J Sutton, D J Fear, H J Gould
• Journal: Allergy (Allergy) Vol. 70 Issue 10 Pg. 1269-77 (Oct 2015) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 26109279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

Chemical References

• CD40 Antigens
• Interleukin-4
• Immunoglobulin E

Topics

• B-Lymphocyte Subsets (immunology, metabolism)
• CD40 Antigens (antagonists & inhibitors, metabolism)
• Cell Survival (immunology)
• Cells, Cultured
• Germinal Center (cytology)
• Humans
• Immunoglobulin Class Switching (genetics, immunology)
• Immunoglobulin E (genetics, immunology)
• Immunologic Memory
• Interleukin-4 (metabolism)
• Lymphocyte Activation (genetics, immunology)
• Lymphocyte Count
• Palatine Tonsil (cytology)
• Signal Transduction