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Open AccessArticle

IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

1
Research & Development Department, Cellular Technology Limited, Shaker Heights, OH 44122, USA
2
Institute of Anatomy and Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 433; https://doi.org/10.3390/cells9020433 (registering DOI)
Received: 3 December 2019 / Revised: 7 February 2020 / Accepted: 12 February 2020 / Published: 13 February 2020
(This article belongs to the Section Cellular Immunology)
Detection of antigen-specific memory B cells for immune monitoring requires their activation, and is commonly accomplished through stimulation with the TLR7/8 agonist R848 and IL-2. To this end, we evaluated whether addition of IL-21 would further enhance this TLR-driven stimulation approach; which it did not. More importantly, as most antigen-specific B cell responses are T cell-driven, we sought to devise a polyclonal B cell stimulation protocol that closely mimics T cell help. Herein, we report that the combination of agonistic anti-CD40, IL-4 and IL-21 affords polyclonal B cell stimulation that was comparable to R848 and IL-2 for detection of influenza-specific memory B cells. An additional advantage of anti-CD40, IL-4 and IL-21 stimulation is the selective activation of IgM+ memory B cells, as well as the elicitation of IgE+ ASC, which the former fails to do. Thereby, we introduce a protocol that mimics physiological B cell activation through helper T cells, including induction of all Ig classes, for immune monitoring of antigen-specific B cell memory.
Keywords: antibody-secreting cells; B cell activation; plasmablasts; IgE; ELISPOT; ImmunoSpot; Fluorospot; immunoglobulin classes; influenza; type 1 allergy antibody-secreting cells; B cell activation; plasmablasts; IgE; ELISPOT; ImmunoSpot; Fluorospot; immunoglobulin classes; influenza; type 1 allergy
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MDPI and ACS Style

Franke, F.; Kirchenbaum, G.A.; Kuerten, S.; Lehmann, P.V. IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells. Cells 2020, 9, 433.

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